Rossmann-fold NAD(P)(+)-binding proteins; A large family of proteins that share a Rossmann-fold NAD(P)H/NAD(P)(+) binding (NADB) domain. The NADB domain is found in numerous dehydrogenases of metabolic pathways such as glycolysis, and many other redox enzymes. NAD binding involves numerous hydrogen-bonds and van der Waals contacts, in particular H-bonding of residues in a turn between the first strand and the subsequent helix of the Rossmann-fold topology. Characteristically, this turn exhibits a consensus binding pattern similar to GXGXXG, in which the first 2 glycines participate in NAD(P)-binding, and the third facilitates close packing of the helix to the beta-strand. Typically, proteins in this family contain a second domain in addition to the NADB domain, which is responsible for specifically binding a substrate and catalyzing a particular enzymatic reaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQFSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:cd05324    1 KVALVTGANRGIGFEIVRQLAKSGPGTVILTARDVERGQAAVEKLRAEGLSVRFHQLDVTDDASIEAAADFVEEKYGGLD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 768021838  86 VLVNNAAVAFKS-DDPMPFDIKAEMTLKTNFFATRNMCNELLPIMKP 131
Cdd:cd05324   81 ILVNNAGIAFKGfDDSTPTREQARETMKTNFFGTVDVTQALLPLLKK 127

Porcine testicular carbonyl reductase (PTCR)-like, classical (c) SDRs; PTCR is a classical SDR which catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. Unlike most SDRs, PTCR functions as a monomer. This subgroup also includes human carbonyl reductase 1 (CBR1) and CBR3. CBR1 is an NADPH-dependent SDR with broad substrate specificity and may be responsible for the in vivo reduction of quinones, prostaglandins, and other carbonyl-containing compounds. In addition it includes poppy NADPH-dependent salutaridine reductase which catalyzes the stereospecific reduction of salutaridine to 7(S)-salutaridinol in the biosynthesis of morphine, and Arabidopsis SDR1,a menthone reductase, which catalyzes the reduction of menthone to neomenthol, a compound with antimicrobial activity; SDR1 can also carry out neomenthol oxidation. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQFSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:cd05324    1 KVALVTGANRGIGFEIVRQLAKSGPGTVILTARDVERGQAAVEKLRAEGLSVRFHQLDVTDDASIEAAADFVEEKYGGLD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 768021838  86 VLVNNAAVAFKS-DDPMPFDIKAEMTLKTNFFATRNMCNELLPIMKP 131
Cdd:cd05324   81 ILVNNAGIAFKGfDDSTPTREQARETMKTNFFGTVDVTQALLPLLKK 127

short chain dehydrogenase; This family contains a wide variety of dehydrogenases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838    6 RVALVTGANRGIGLAIARELCRQfSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKE-GAKVVLVDRSEEKLEAVAKELGALGGKALFIQGDVTDRAQVKALVEQAVERLGRLD 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 768021838   86 VLVNNAAVA----FKSDDPMpfDIKAEMtlKTNFFATRNMCNELLPIMK 130
Cdd:pfam00106  80 ILVNNAGITglgpFSELSDE--DWERVI--DVNLTGVFNLTRAVLPAMI 124

This enzymatic domain is part of bacterial polyketide synthases; It catalyses the first step in the reductive modification of the beta-carbonyl centres in the growing polyketide chain. It uses NADPH to reduce the keto group to a hydroxy group.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838     9 LVTGANRGIGLAIARELCRQFSGDVVLTAR--DVARGQAA-VQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:smart00822   4 LITGGLGGLGRALARWLAERGARRLVLLSRsgPDAPGAAAlLAELEAAGARVTVVACDVADRDALAAVLAAIPAVEGPLT 83

                   ....*...
gi 768021838    86 VLVNNAAV 93
Cdd:smart00822  84 GVIHAAGV 91

Porcine testicular carbonyl reductase (PTCR)-like, classical (c) SDRs; PTCR is a classical SDR which catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. Unlike most SDRs, PTCR functions as a monomer. This subgroup also includes human carbonyl reductase 1 (CBR1) and CBR3. CBR1 is an NADPH-dependent SDR with broad substrate specificity and may be responsible for the in vivo reduction of quinones, prostaglandins, and other carbonyl-containing compounds. In addition it includes poppy NADPH-dependent salutaridine reductase which catalyzes the stereospecific reduction of salutaridine to 7(S)-salutaridinol in the biosynthesis of morphine, and Arabidopsis SDR1,a menthone reductase, which catalyzes the reduction of menthone to neomenthol, a compound with antimicrobial activity; SDR1 can also carry out neomenthol oxidation. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQFSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:cd05324    1 KVALVTGANRGIGFEIVRQLAKSGPGTVILTARDVERGQAAVEKLRAEGLSVRFHQLDVTDDASIEAAADFVEEKYGGLD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 768021838  86 VLVNNAAVAFKS-DDPMPFDIKAEMTLKTNFFATRNMCNELLPIMKP 131
Cdd:cd05324   81 ILVNNAGIAFKGfDDSTPTREQARETMKTNFFGTVDVTQALLPLLKK 127

Short-chain dehydrogenase [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   1 MSSCSRVALVTGANRGIGLAIARELCRQfsG-DVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRK 79
Cdd:COG0300    1 MSLTGKTVLITGASSGIGRALARALAAR--GaRVVLVARDAERLEALAAELRAAGARVEVVALDVTDPDAVAALAEAVLA 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 768021838  80 EYGGLNVLVNNAAVAfksdDPMPF-DIKAEM---TLKTNFFATRNMCNELLPIMK 130
Cdd:COG0300   79 RFGPIDVLVNNAGVG----GGGPFeELDLEDlrrVFEVNVFGPVRLTRALLPLMR 129

short chain dehydrogenase; This family contains a wide variety of dehydrogenases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838    6 RVALVTGANRGIGLAIARELCRQfSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:pfam00106   1 KVALVTGASSGIGRAIAKRLAKE-GAKVVLVDRSEEKLEAVAKELGALGGKALFIQGDVTDRAQVKALVEQAVERLGRLD 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 768021838   86 VLVNNAAVA----FKSDDPMpfDIKAEMtlKTNFFATRNMCNELLPIMK 130
Cdd:pfam00106  80 ILVNNAGITglgpFSELSDE--DWERVI--DVNLTGVFNLTRAVLPAMI 124

Short-chain dehydrogenase involved in D-alanine esterification of teichoic acids [Cell wall/membrane/envelope biogenesis, Lipid transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   9 LVTGANRGIGLAIARelcrQFSG---DVVLTARDVARGQAAVQQLqaeglsPRFH--QLDIDDLQSIRALRDFLRKEYGG 83
Cdd:COG3967    9 LITGGTSGIGLALAK----RLHArgnTVIITGRREEKLEEAAAAN------PGLHtiVLDVADPASIAALAEQVTAEFPD 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768021838  84 LNVLVNNAAVA----FKSDDPMPFDIKAEMTlkTNFFATRNMCNELLPIMK--PHAA 134
Cdd:COG3967   79 LNVLINNAGIMraedLLDEAEDLADAEREIT--TNLLGPIRLTAAFLPHLKaqPEAA 133

short chain dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   5 SRVALVTGANRGIGLAIARELCRQfSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGL 84
Cdd:PRK12939   7 GKRALVTGAARGLGAAFAEALAEA-GATVAFNDGLAAEARELAAALEAAGGRAHAIAADLADPASVQRFFDAAAAALGGL 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 768021838  85 NVLVNNAAVAfKSDDPMPFDIKA-EMTLKTNFFATRNMCNELLPIMK 130
Cdd:PRK12939  86 DGLVNNAGIT-NSKSATELDIDTwDAVMNVNVRGTFLMLRAALPHLR 131

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQfSGDVVLTARDVARGQAAVQQLQAEGLSpRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:PRK07231   6 KVAIVTGASSGIGEGIARRFAAE-GARVVVTDRNEEAAERVAAEILAGGRA-IAVAADVSDEADVEAAVAAALERFGSVD 83

                 ....*.
gi 768021838  86 VLVNNA 91
Cdd:PRK07231  84 ILVNNA 89

retinol dehydrogenase (retinol-DH), Light dependent Protochlorophyllide (Pchlide) OxidoReductase (LPOR) and related proteins, classical (c) SDRs; Classical SDR subgroup containing retinol-DHs, LPORs, and related proteins. Retinol is processed by a medium chain alcohol dehydrogenase followed by retinol-DHs. Pchlide reductases act in chlorophyll biosynthesis. There are distinct enzymes that catalyze Pchlide reduction in light or dark conditions. Light-dependent reduction is via an NADP-dependent SDR, LPOR. Proteins in this subfamily share the glycine-rich NAD-binding motif of the classical SDRs, have a partial match to the canonical active site tetrad, but lack the typical active site Ser. This subgroup includes the human proteins: retinol dehydrogenase -12, -13 ,and -14, dehydrogenase/reductase SDR family member (DHRS)-12 , -13 and -X (a DHRS on chromosome X), and WWOX (WW domain-containing oxidoreductase), as well as a Neurospora crassa SDR encoded by the blue light inducible bli-4 gene. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQfSGDVVLTARDVARGQAAVQQLQAEGLSPR--FHQLDIDDLQSIRALRDFLRKEYGG 83
Cdd:cd05327    2 KVVVITGANSGIGKETARELAKR-GAHVIIACRNEEKGEEAAAEIKKETGNAKveVIQLDLSSLASVRQFAEEFLARFPR 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 768021838  84 LNVLVNNAAV----AFKSDDPMpfdikaEMTLKTNFFATRNMCNELLPIMK 130
Cdd:cd05327   81 LDILINNAGImappRRLTKDGF------ELQFAVNYLGHFLLTNLLLPVLK 125

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQFSGDVVLTARDVARgqaavqqlqAEGLSPRFH--QLDIDDLQSIRALRDFLrkeyGG 83
Cdd:PRK08264   7 KVVLVTGANRGIGRAFVEQLLARGAAKVYAAARDPES---------VTDLGPRVVplQLDVTDPASVAAAAEAA----SD 73

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 768021838  84 LNVLVNNAAV----AFKSDDPMPfDIKAEMtlKTNFFATRNMCNELLPIMK 130
Cdd:PRK08264  74 VTILVNNAGIfrtgSLLLEGDED-ALRAEM--ETNYFGPLAMARAFAPVLA 121

beta-Keto acyl carrier protein reductase (BKR), involved in Type II FAS, classical (c) SDRs; This subgroup includes the Escherichai coli K12 BKR, FabG. BKR catalyzes the NADPH-dependent reduction of ACP in the first reductive step of de novo fatty acid synthesis (FAS). FAS consists of four elongation steps, which are repeated to extend the fatty acid chain through the addition of two-carbo units from malonyl acyl-carrier protein (ACP): condensation, reduction, dehydration, and a final reduction. Type II FAS, typical of plants and many bacteria, maintains these activities on discrete polypeptides, while type I FAS utilizes one or two multifunctional polypeptides. BKR resembles enoyl reductase, which catalyzes the second reduction step in FAS. SDRs are a functionally diverse family of oxidoreductases that have a single domain with structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet) NAD(P)(H) binding region and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H) binding pattern: TGxxxGxG in classical SDRs. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P) binding motif and an altered active site motif (YXXXN). Fungal type type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P) binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr-151 and Lys-155, and well as Asn-111 (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQfSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:cd05333    1 KVALVTGASRGIGRAIALRLAAE-GAKVAVTDRSEEAAAETVEEIKALGGNAAALEADVSDREAVEALVEKVEAEFGPVD 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 768021838  86 VLVNNA-------AVAFKSDDpmpFDikaeMTLKTNFFATRNMCNELLPIM 129
Cdd:cd05333   80 ILVNNAgitrdnlLMRMSEED---WD----AVINVNLTGVFNVTQAVIRAM 123

classical (c) SDR, subgroup 2; Short-chain dehydrogenases/reductases (SDRs, aka Tyrosine-dependent oxidoreductases) are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   1 MSSCSRVALVTGANRGIGLAIARELcRQFSGDVVLTARDvargQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKE 80
Cdd:cd05370    1 MKLTGNTVLITGGTSGIGLALARKF-LEAGNTVIITGRR----EERLAEAKKELPNIHTIVLDVGDAESVEALAEALLSE 75

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 768021838  81 YGGLNVLVNNAAVAFKSD--DPMPFDIKAEMTLKTNFFATRNMCNELLPIMK 130
Cdd:cd05370   76 YPNLDILINNAGIQRPIDlrDPASDLDKADTEIDTNLIGPIRLIKAFLPHLK 127

3-ketoacyl-(acyl-carrier-protein) reductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQ-FsgDVVLTA-RDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGG 83
Cdd:PRK12745   3 PVALVTGGRRGIGLGIARALAAAgF--DLAINDrPDDEELAATQQELRALGVEVIFFPADVADLSAHEAMLDAAQAAWGR 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768021838  84 LNVLVNNAAVAFKSDD------PMPFDIKAEMTLKTNFFATRNMCNELLPIMKPHAAKF 136
Cdd:PRK12745  81 IDCLVNNAGVGVKVRGdlldltPESFDRVLAINLRGPFFLTQAVAKRMLAQPEPEELPH 139

putative beta-ketoacyl acyl carrier protein [ACP] reductase (BKR)-like, SDR; This subgroup resembles the SDR family, but does not have a perfect match to the NAD-binding motif or the catalytic tetrad characteristic of the SDRs. It includes the SDRs, Q9HYA2 from Pseudomonas aeruginosa PAO1 and APE0912 from Aeropyrum pernix K1. BKR catalyzes the NADPH-dependent reduction of ACP in the first reductive step of de novo fatty acid synthesis (FAS). FAS consists of four elongation steps, which are repeated to extend the fatty acid chain through the addition of two-carbo units from malonyl acyl-carrier protein (ACP): condensation, reduction, dehydration, and a final reduction. Type II FAS, typical of plants and many bacteria, maintains these activities on discrete polypeptides, while type I FAS utilizes one or two multifunctional polypeptides. BKR resembles enoyl reductase, which catalyzes the second reduction step in FAS. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQFSgDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:cd05344    2 KVALVTAASSGIGLAIARALAREGA-RVAICARNRENLERAASELRAGGAGVLAVVADLTDPEDIDRLVEKAGDAFGRVD 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 768021838  86 VLVNNA------AVAFKSDDpmpfDIKAEMTLKtnFFATRNMCNELLPIMK 130
Cdd:cd05344   81 ILVNNAggpppgPFAELTDE----DWLEAFDLK--LLSVIRIVRAVLPGMK 125

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQfSGDVVLTARDVARGQAAVQQLQAEGLSPRFH--QLDIDDLQSIRALRDFLrKEYGG 83
Cdd:PRK06914   4 KIAIVTGASSGFGLLTTLELAKK-GYLVIATMRNPEKQENLLSQATQLNLQQNIKvqQLDVTDQNSIHNFQLVL-KEIGR 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768021838  84 LNVLVNNAAVA---FKSDDPM-----PFDikaemtlkTNFFATRNMCNELLPIMKPH 132
Cdd:PRK06914  82 IDLLVNNAGYAnggFVEEIPVeeyrkQFE--------TNVFGAISVTQAVLPYMRKQ 130

tetrahydroxynaphthalene/trihydroxynaphthalene reductase-like, classical (c) SDRs; 1,3,6,8-tetrahydroxynaphthalene reductase (4HNR) of Magnaporthe grisea and the related 1,3,8-trihydroxynaphthalene reductase (3HNR) are typical members of the SDR family containing the canonical glycine rich NAD(P)-binding site and active site tetrad, and function in fungal melanin biosynthesis. This subgroup also includes an SDR from Norway spruce that may function to protect against both biotic and abitoic stress. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQFSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:cd05362    4 KVALVTGASRGIGRAIAKRLARDGASVVVNYASSKAAAEEVVAEIEAAGGKAIAVQADVSDPSQVARLFDAAEKAFGGVD 83

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 768021838  86 VLVNNAAVAFKSD----DPMPFDIKAEMTLKTNFFATR 119
Cdd:cd05362   84 ILVNNAGVMLKKPiaetSEEEFDRMFTVNTKGAFFVLQ 121

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRqFSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQL--DIDDLQSIRALRDFLRKEYGG 83
Cdd:PRK09242  10 QTALITGASKGIGLAIAREFLG-LGADVLIVARDADALAQARDELAEEFPEREVHGLaaDVSDDEDRRAILDWVEDHWDG 88

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 768021838  84 LNVLVNNAA--VAFKSDDPMPFDIKAemTLKTNFFATRNMCNELLPIMKPHAA 134
Cdd:PRK09242  89 LHILVNNAGgnIRKAAIDYTEDEWRG--IFETNLFSAFELSRYAHPLLKQHAS 139

3beta17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; This subgroup includes members identified as 3beta17beta hydroxysteroid dehydrogenase, 20beta hydroxysteroid dehydrogenase, and R-alcohol dehydrogenase. These proteins exhibit the canonical active site tetrad and glycine rich NAD(P)-binding motif of the classical SDRs. 17beta-dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens, and include members of the SDR family. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQfSGDVVLTARDVARGQAAVQQLqaeGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:cd05341    6 KVAIVTGGARGLGLAHARLLVAE-GAKVVLSDILDEEGQAAAAEL---GDAARFFHLDVTDEDGWTAVVDTAREAFGRLD 81

                 ....*....
gi 768021838  86 VLVNNAAVA 94
Cdd:cd05341   82 VLVNNAGIL 90

putative beta-ketoacyl acyl carrier protein [ACP] reductase (BKR), subgroup 1, classical (c) SDR; This subgroup includes Escherichia coli CFT073 FabG. The Escherichai coli K12 BKR, FabG, belongs to a different subgroup. BKR catalyzes the NADPH-dependent reduction of ACP in the first reductive step of de novo fatty acid synthesis (FAS). FAS consists of four elongation steps, which are repeated to extend the fatty acid chain through the addition of two-carbo units from malonyl acyl-carrier protein (ACP): condensation, reduction, dehydration, and a final reduction. Type II FAS, typical of plants and many bacteria, maintains these activities on discrete polypeptides, while type I FAS utilizes one or two multifunctional polypeptides. BKR resembles enoyl reductase, which catalyzes the second reduction step in FAS. SDRs are a functionally diverse family of oxidoreductases that have a single domain with structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet) NAD(P)(H) binding region and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H) binding pattern: TGxxxGxG in classical SDRs. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P) binding motif and an altered active site motif (YXXXN). Fungal type type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P) binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr-151 and Lys-155, and well as Asn-111 (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQFSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:cd05337    2 PVAIVTGASRGIGRAIATELAARGFDIAINDLPDDDQATEVVAEVLAAGRRAIYFQADIGELSDHEALLDQAWEDFGRLD 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 768021838  86 VLVNNAAVAFKSD------DPMPFDIKAEMTLKTNFFATRNMCNELL 126
Cdd:cd05337   82 CLVNNAGIAVRPRgdlldlTEDSFDRLIAINLRGPFFLTQAVARRMV 128

gluconate 5-dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELcRQFSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:PRK07523  11 RRALVTGSSQGIGYALAEGL-AQAGAEVILNGRDPAKLAAAAESLKGQGLSAHALAFDVTDHDAVRAAIDAFEAEIGPID 89

                         90       100       110
                 ....*....|....*....|....*....|
gi 768021838  86 VLVNNAAVAFKSD-DPMPFDiKAEMTLKTN 114
Cdd:PRK07523  90 ILVNNAGMQFRTPlEDFPAD-AFERLLRTN 118

SDR family oxidoreductase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCrQFSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:PRK07035   9 KIALVTGASRGIGEAIAKLLA-QQGAHVIVSSRKLDGCQAVADAIVAAGGKAEALACHIGEMEQIDALFAHIRERHGRLD 87

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 768021838  86 VLVNNAAV-----AFKSDDPMPFDIKAEMTLKTNFFatrnMCNELLPIMK 130
Cdd:PRK07035  88 ILVNNAAAnpyfgHILDTDLGAFQKTVDVNIRGYFF----MSVEAGKLMK 133

HetN oxidoreductase-like, classical (c) SDR; This subgroup includes Anabaena sp. strain PCC 7120 HetN, a putative oxidoreductase involved in heterocyst differentiation, and related proteins. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQfSGDVVLTARDvargQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:cd08932    1 KVALVTGASRGIGIEIARALARD-GYRVSLGLRN----PEDLAALSASGGDVEAVPYDARDPEDARALVDALRDRFGRID 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 768021838  86 VLVNNAAVAFKS--DDPMPFDIKAemTLKTNFFATRNMCNELLPIM 129
Cdd:cd08932   76 VLVHNAGIGRPTtlREGSDAELEA--HFSINVIAPAELTRALLPAL 119

human dehydrogenase/reductase (SDR family) member 1 (DHRS1) and human hydroxysteroid dehydrogenase-like protein 2 (HSDL2), classical (c) SDRs; This subgroup includes human DHRS1 and human HSDL2 and related proteins. These are members of the classical SDR family, with a canonical Gly-rich NAD-binding motif and the typical YXXXK active site motif. However, the rest of the catalytic tetrad is not strongly conserved. DHRS1 mRNA has been detected in many tissues, liver, heart, skeletal muscle, kidney and pancreas; a longer transcript is predominantly expressed in the liver , a shorter one in the heart. HSDL2 may play a part in fatty acid metabolism, as it is found in peroxisomes. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRS are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes have a 3-glycine N-terminal NAD(P)(H)-binding pattern (typically, TGxxxGxG in classical SDRs and TGxxGxxG in extended SDRs), while substrate binding is in the C-terminal region. A critical catalytic Tyr residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering), is often found in a conserved YXXXK pattern. In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) or additional Ser, contributing to the active site. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving the conserved Tyr and Lys, as well as Asn (or Ser). Some SDR family members, including 17 beta-hydroxysteroid dehydrogenase contain an additional helix-turn-helix motif that is not generally found among SDRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQfSGDVVLTARDVARG------------QAAVQQLQAEGLSPRFHQLDIDDLQSIRAL 73
Cdd:cd05338    4 KVAFVTGASRGIGRAIALRLAKA-GATVVVAAKTASEGdngsakslpgtiEETAEEIEAAGGQALPIVVDVRDEDQVRAL 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768021838  74 RDFLRKEYGGLNVLVNNAAVAFKSD-DPMP---FDIKAEMTLKTNFFATRNMCNELLPIMKPH 132
Cdd:cd05338   83 VEATVDQFGRLDILVNNAGAIWLSLvEDTPakrFDLMQRVNLRGTYLLSQAALPHMVKAGQGH 145

3-ketoacyl-(acyl-carrier-protein) reductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   6 RVALVTGANRGIGLAIARELCRQFSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLN 85
Cdd:PRK05565   6 KVAIVTGASGGIGRAIAELLAKEGAKVVIAYDINEEAAQELLEEIKEEGGDAIAVKADVSSEEDVENLVEQIVEKFGKID 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 768021838  86 VLVNNAAVafksddpMPFDIKAEMTLK-------TNFFATRNMCNELLPIMK 130
Cdd:PRK05565  86 ILVNNAGI-------SNFGLVTDMTDEewdrvidVNLTGVMLLTRYALPYMI 130

light-dependent protochlorophyllide reductase (LPOR)-like, classical (c)-like SDRs; Classical SDR-like subgroup containing LPOR and related proteins. Protochlorophyllide (Pchlide) reductases act in chlorophyll biosynthesis. There are distinct enzymes that catalyze Pchlide reduction in light or dark conditions. Light-dependent reduction is via an NADP-dependent SDR, LPOR. Proteins in this subfamily share the glycine-rich NAD-binding motif of the classical SDRs, have a partial match to the canonical active site tetrad, but lack the typical active site Ser. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768021838   8 ALVTGANRGIGLAIARELCRQFSGDVVLTARDVARGQAAVQQLQAEGLSPRFHQLDIDDLQSIRALRDFLRKEYGGLNVL 87
Cdd:cd09810    4 VVITGASSGLGLAAAKALARRGEWHVVMACRDFLKAEQAAQEVGMPKDSYSVLHCDLASLDSVRQFVDNFRRTGRPLDAL 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 768021838  88 VNNAAVAFKSDDPMPFDIKA-EMTLKTNFFATRNMCNELL 126
Cdd:cd09810   84 VCNAAVYLPTAKEPRFTADGfELTVGVNHLGHFLLTNLLL 123