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 2217313779   6 MERWRDRLALVTGASGGIGAAVARALVQQGLKVVGCARTVGNIE------------------------------------ 49
Cdd:cd05343     1 MERWRGRVALVTGASVGIGAAVARALVQHGMKVVGCARRVDKIEalaaecqsagyptlfpyqcdlsneeqilsmfsairt 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  50 ---------------------------------VNVLALSICTREAYQSMKERNVDDGHIININSMSGHRVLPLSVTHFY 96
Cdd:cd05343    81 qhqgvdvcinnaglarpepllsgktegwkemfdVNVLALSICTREAYQSMKERNVDDGHIININSMSGHRVPPVSVFHFY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  97 SATKYAVTALTEGLRQELREAQTHIRAT-------------------------------CLKPEDVAEAVIYVLSTPAHI 145
Cdd:cd05343   161 AATKHAVTALTEGLRQELREAKTHIRATsispglvetefafklhdndpekaaatyesipCLKPEDVANAVLYVLSTPPHV 240

                         250
                  ....*....|
gi 2217313779 146 QIGDIQMRPT 155
Cdd:cd05343   241 QIHDILLRPT 250

human Mgc4172-like, classical (c) SDRs; Human Mgc4172-like proteins, putative SDRs. These proteins are members of the SDR family, with a canonical active site tetrad and a typical Gly-rich NAD-binding motif. 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 2217313779   6 MERWRDRLALVTGASGGIGAAVARALVQQGLKVVGCARTVGNIE------------------------------------ 49
Cdd:cd05343     1 MERWRGRVALVTGASVGIGAAVARALVQHGMKVVGCARRVDKIEalaaecqsagyptlfpyqcdlsneeqilsmfsairt 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  50 ---------------------------------VNVLALSICTREAYQSMKERNVDDGHIININSMSGHRVLPLSVTHFY 96
Cdd:cd05343    81 qhqgvdvcinnaglarpepllsgktegwkemfdVNVLALSICTREAYQSMKERNVDDGHIININSMSGHRVPPVSVFHFY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  97 SATKYAVTALTEGLRQELREAQTHIRAT-------------------------------CLKPEDVAEAVIYVLSTPAHI 145
Cdd:cd05343   161 AATKHAVTALTEGLRQELREAKTHIRATsispglvetefafklhdndpekaaatyesipCLKPEDVANAVLYVLSTPPHV 240

                         250
                  ....*....|
gi 2217313779 146 QIGDIQMRPT 155
Cdd:cd05343   241 QIHDILLRPT 250

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  14 ALVTGASGGIGAAVARALVQQGLKVVGCART------------------------------------------------V 45
Cdd:pfam00106   3 ALVTGASSGIGRAIAKRLAKEGAKVVLVDRSeekleavakelgalggkalfiqgdvtdraqvkalveqaverlgrldilV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  46 GN--------------------IEVNVLALSICTREAYQSMKERNVddGHIININSMSGHRVLPLSVThfYSATKYAVTA 105
Cdd:pfam00106  83 NNagitglgpfselsdedwervIDVNLTGVFNLTRAVLPAMIKGSG--GRIVNISSVAGLVPYPGGSA--YSASKAAVIG 158

                         170       180
                  ....*....|....*....|...
gi 2217313779 106 LTEGLRQELreAQTHIRATCLKP 128
Cdd:pfam00106 159 FTRSLALEL--APHGIRVNAVAP 179

SDR family mycofactocin-dependent oxidoreductase; Members of this protein subfamily are putative oxidoreductases belonging to the larger SDR family. All members occur in genomes that encode a cassette for the biosynthesis of mycofactocin, a proposed electron carrier of a novel redox pool. Characterized members of this family are described as NDMA-dependent, meaning that a blue aniline dye serving as an artificial electron acceptor is required for members of this family to cycle in vitro, since the bound NAD residue is not exchangeable. This family resembles TIGR03971 most closely in the N-terminal region, consistent with the published hypothesis of NAD interaction with mycofactocin. See EC 1.1.99.36. [Unknown function, Enzymes of unknown specificity]

                          10        20
                  ....*....|....*....|....*...
gi 2217313779  12 RLALVTGASGGIGAAVARALVQQGLKVV 39
Cdd:TIGR04504   2 RVALVTGAARGIGAATVRRLAADGWRVV 29

human Mgc4172-like, classical (c) SDRs; Human Mgc4172-like proteins, putative SDRs. These proteins are members of the SDR family, with a canonical active site tetrad and a typical Gly-rich NAD-binding motif. 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 2217313779   6 MERWRDRLALVTGASGGIGAAVARALVQQGLKVVGCARTVGNIE------------------------------------ 49
Cdd:cd05343     1 MERWRGRVALVTGASVGIGAAVARALVQHGMKVVGCARRVDKIEalaaecqsagyptlfpyqcdlsneeqilsmfsairt 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  50 ---------------------------------VNVLALSICTREAYQSMKERNVDDGHIININSMSGHRVLPLSVTHFY 96
Cdd:cd05343    81 qhqgvdvcinnaglarpepllsgktegwkemfdVNVLALSICTREAYQSMKERNVDDGHIININSMSGHRVPPVSVFHFY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  97 SATKYAVTALTEGLRQELREAQTHIRAT-------------------------------CLKPEDVAEAVIYVLSTPAHI 145
Cdd:cd05343   161 AATKHAVTALTEGLRQELREAKTHIRATsispglvetefafklhdndpekaaatyesipCLKPEDVANAVLYVLSTPPHV 240

                         250
                  ....*....|
gi 2217313779 146 QIGDIQMRPT 155
Cdd:cd05343   241 QIHDILLRPT 250

classical (c) SDR, subgroup 5; These proteins are members of the classical SDR family, with a canonical active site tetrad and a typical Gly-rich NAD-binding motif. 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 2217313779  14 ALVTGASGGIGAAVARALVQQGLKVVGCART------------------------------------------------- 44
Cdd:cd05346     3 VLITGASSGIGEATARRFAKAGAKLILTGRRaerlqeladelgakfpvkvlplqldvsdresieaalenlpeefrdidil 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  45 VGN---------------------IEVNVLALSICTREAYQSMKERNvdDGHIININSMSGHRVLPLSvtHFYSATKYAV 103
Cdd:cd05346    83 VNNaglalgldpaqeadledwetmIDTNVKGLLNVTRLILPIMIARN--QGHIINLGSIAGRYPYAGG--NVYCATKAAV 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779 104 TALTEGLRQELreAQTHIRAT-------------------------------CLKPEDVAEAVIYVLSTPAHIQIGDIQM 152
Cdd:cd05346   159 RQFSLNLRKDL--IGTGIRVTniepglvetefslvrfhgdkekadkvyegvePLTPEDIAETILWVASRPAHVNINDIEI 236

                  ....*
gi 2217313779 153 RPTEQ 157
Cdd:cd05346   237 MPVNQ 241

classical (c) SDRs; 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 prostaglandin dehydrogenase (PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, PGDH numbering) and/or an Asn (Asn-107, 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 2217313779  14 ALVTGASGGIGAAVARALVQQGLKVVGCARTVGN---------------------------------------------- 47
Cdd:cd05233     1 ALVTGASSGIGRAIARRLAREGAKVVLADRNEEAlaelaaiealggnavavqadvsdeedvealveealeefgrldilvn 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  48 ---------------------IEVNVLALSICTREAYQSMKERNvdDGHIININSMSGHRVLPLSVThfYSATKYAVTAL 106
Cdd:cd05233    81 nagiarpgpleeltdedwdrvLDVNLTGVFLLTRAALPHMKKQG--GGRIVNISSVAGLRPLPGQAA--YAASKAALEGL 156

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779 107 TEGLRQELreAQTHIRATCL--------------------------------KPEDVAEAVIYVLSTPAH 144
Cdd:cd05233   157 TRSLALEL--APYGIRVNAVapglvdtpmlaklgpeeaekelaaaiplgrlgTPEEVAEAVVFLASDEAS 224

NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family [Lipid transport and metabolism]; NAD(P)-dependent dehydrogenase, short-chain alcohol dehydrogenase family is part of the Pathway/BioSystem: Fatty acid biosynthesis

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779   6 MERWRDRLALVTGASGGIGAAVARALVQQGLKVVGCART----------------------------------------- 44
Cdd:COG1028     1 MTRLKGKVALVTGGSSGIGRAIARALAAEGARVVITDRDaealeaaaaelraaggralavaadvtdeaavealvaaavaa 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  45 -------VGN--------------------IEVNVLALSICTREAYQSMKERnvDDGHIININSMSGHRVLPLSVthFYS 97
Cdd:COG1028    81 fgrldilVNNagitppgpleelteedwdrvLDVNLKGPFLLTRAALPHMRER--GGGRIVNISSIAGLRGSPGQA--AYA 156

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2217313779  98 ATKYAVTALTEGLRQELreAQTHIRATCL---------------------------------KPEDVAEAVIYVLSTPA 143
Cdd:COG1028   157 ASKAAVVGLTRSLALEL--APRGIRVNAVapgpidtpmtrallgaeevrealaariplgrlgTPEEVAAAVLFLASDAA 233

17beta hydroxysteroid dehydrogenase-like, classical (c) SDRs; 17beta-hydroxysteroid dehydrogenases are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. 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 2217313779  14 ALVTGASGGIGAAVARALVQQGLKVVGCARTVGNIE-------VNVLALSI----------------------------- 57
Cdd:cd05374     3 VLITGCSSGIGLALALALAAQGYRVIATARNPDKLEslgellnDNLEVLELdvtdeesikaavkevierfgridvlvnna 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  58 ----------CTREAYQSMKERNV-----------------DDGHIININSMSGHRVLPLsvTHFYSATKYAVTALTEGL 110
Cdd:cd05374    83 gyglfgpleeTSIEEVRELFEVNVfgplrvtraflplmrkqGSGRIVNVSSVAGLVPTPF--LGPYCASKAALEALSESL 160

                         170
                  ....*....|....*...
gi 2217313779 111 RQELreAQTHIRATCLKP 128
Cdd:cd05374   161 RLEL--APFGIKVTIIEP 176

classical (c) SDR, subgroup 4; This subgroup has a canonical active site tetrad and a typical Gly-rich NAD-binding motif. 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 2217313779  14 ALVTGASGGIGAAVARALVQQGLKVVGCARTVGNIEV-------NVLALSICTRE------AYQSMKE------------ 68
Cdd:cd08929     3 ALVTGASRGIGEATARLLHAEGYRVGICARDEARLAAaaaqeleGVLGLAGDVRDeadvrrAVDAMEEafggldalvnna 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  69 -----------------RNVDD---------------------GHIININSMSGhrVLPLSVTHFYSATKYAVTALTEGL 110
Cdd:cd08929    83 gvgvmkpveeltpeewrLVLDTnltgafycihkaapallrrggGTIVNVGSLAG--KNAFKGGAAYNASKFGLLGLSEAA 160

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217313779 111 RQELREAqtHIRATC--------------------LKPEDVAEAVIYVLSTPAHIQIGDIQMRPT 155
Cdd:cd08929   161 MLDLREA--NIRVVNvmpgsvdtgfagspegqawkLAPEDVAQAVLFALEMPARALVSRIELRPT 223

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 2217313779  12 RLALVTGASGGIGAAVARALVQQGLKVVGCAR-------------------------------------TVGNIE----- 49
Cdd:cd08932     1 KVALVTGASRGIGIEIARALARDGYRVSLGLRnpedlaalsasggdveavpydardpedaralvdalrdRFGRIDvlvhn 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  50 ----------------------VNVLALSICTREAYQSMKERNvdDGHIININSMSGHRVLPLSVThfYSATKYAVTALT 107
Cdd:cd08932    81 agigrpttlregsdaeleahfsINVIAPAELTRALLPALREAG--SGRVVFLNSLSGKRVLAGNAG--YSASKFALRALA 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217313779 108 EGLRQElrEAQTHIRAT--CL-----------------------KPEDVAEAVIYVLSTPAHI 145
Cdd:cd08932   157 HALRQE--GWDHGVRVSavCPgfvdtpmaqgltlvgafppeemiQPKDIANLVRMVIELPENI 217

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  12 RLALVTGASGGIGAAVARAL------------------VQQGLK---------------------------VVGCA---- 42
Cdd:PRK08219    4 PTALITGASRGIGAAIARELapthtlllggrpaerldeLAAELPgatpfpvdltdpeaiaaaveqlgrldvLVHNAgvad 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  43 -RTVG---------NIEVNVLALSICTREAYQSMKERnvdDGHIININSMSGHRVLPLSVThfYSATKYAVTALTEGLRQ 112
Cdd:PRK08219   84 lGPVAestvdewraTLEVNVVAPAELTRLLLPALRAA---HGHVVFINSGAGLRANPGWGS--YAASKFALRALADALRE 158

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779 113 ELREaqtHIRATC---------------------------LKPEDVAEAVIYVLSTPAHIQIGDIQMRPT 155
Cdd:PRK08219  159 EEPG---NVRVTSvhpgrtdtdmqrglvaqeggeydperyLRPETVAKAVRFAVDAPPDAHITEVVVRPR 225

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  10 RDRLALVTGASGGIGAAVARALVQQGLKVV----------------GCAR------------------------------ 43
Cdd:PRK07825    4 RGKVVAITGGARGIGLATARALAALGARVAigdldealaketaaelGLVVggpldvtdpasfaafldaveadlgpidvlv 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  44 ------------------TVGNIEVNVLALSICTREAYQSMKERNvdDGHIININSMSGHRVLPLSVThfYSATKYAVTA 105
Cdd:PRK07825   84 nnagvmpvgpfldepdavTRRILDVNVYGVILGSKLAAPRMVPRG--RGHVVNVASLAGKIPVPGMAT--YCASKHAVVG 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2217313779 106 LTEGLRQELREAQTHIRATC--------------------LKPEDVAEAVIYVLSTPA 143
Cdd:PRK07825  160 FTDAARLELRGTGVHVSVVLpsfvnteliagtggakgfknVEPEDVAAAIVGTVAKPR 217

human 17-beta-hydroxysteroid dehydrogenase XI-like, classical (c) SDRs; 17-beta-hydroxysteroid dehydrogenases (17betaHSD) are a group of isozymes that catalyze activation and inactivation of estrogen and androgens. 17betaHSD type XI, a classical SDR, preferentially converts 3alpha-Adiol to androsterone but not numerous other tested steroids. This subgroup of classical SDRs also includes members identified as retinol dehydrogenases, which convert retinol to retinal, a property that overlaps with 17betaHSD activity. 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 2217313779  13 LALVTGASGGIGAAVARALVQQGLKVV-------------------------------------GCA----RTVGNI--- 48
Cdd:cd05339     1 IVLITGGGSGIGRLLALEFAKRGAKVVildinekgaeetannvrkaggkvhyykcdvskreevyEAAkkikKEVGDVtil 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  49 ------------------------EVNVLALSICTREAYQSMKERNvdDGHIININSMSGHrVLPLSVTHfYSATKYAVT 104
Cdd:cd05339    81 innagvvsgkkllelpdeeiektfEVNTLAHFWTTKAFLPDMLERN--HGHIVTIASVAGL-ISPAGLAD-YCASKAAAV 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2217313779 105 ALTEGLRQELREAQ-THIRATC------------------------LKPEDVAEAVI 136
Cdd:cd05339   157 GFHESLRLELKAYGkPGIKTTLvcpyfintgmfqgvktprpllapiLEPEYVAEKIV 213

3-oxoacyl-ACP reductase FabG;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  12 RLALVTGASGGIGAAVARALVQQGLKVVGCART----------------------------------------------- 44
Cdd:PRK05653    6 KTALVTGASRGIGRAIALRLAADGAKVVIYDSNeeaaealaaelraaggearvlvfdvsdeaavralieaaveafgaldi 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  45 -VGN--------------------IEVNVLALSICTREAYQSMKERNvdDGHIININSMSGhRVLPLSVTHfYSATKYAV 103
Cdd:PRK05653   86 lVNNagitrdallprmseedwdrvIDVNLTGTFNVVRAALPPMIKAR--YGRIVNISSVSG-VTGNPGQTN-YSAAKAGV 161

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2217313779 104 TALTEGLRQELreAQTHIRATCL-------------------------------KPEDVAEAVIYVLS 140
Cdd:PRK05653  162 IGFTKALALEL--ASRGITVNAVapgfidtdmteglpeevkaeilkeiplgrlgQPEEVANAVAFLAS 227

short chain dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  10 RDRLALVTGASGGIGAAVARALVQQGLKVVGCART------------------------VGNIE---------------- 49
Cdd:PRK07109    7 GRQVVVITGASAGVGRATARAFARRGAKVVLLARGeeglealaaeiraaggealavvadVADAEavqaaadraeeelgpi 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  50 ---VNVLALSIC-------------------------TREAYQSMKERnvDDGHIININSMSGHRVLPLSVThfYSATKY 101
Cdd:PRK07109   87 dtwVNNAMVTVFgpfedvtpeefrrvtevtylgvvhgTLAALRHMRPR--DRGAIIQVGSALAYRSIPLQSA--YCAAKH 162

                         170       180
                  ....*....|....*....|....*..
gi 2217313779 102 AVTALTEGLRQELREAQTHIRATCLKP 128
Cdd:PRK07109  163 AIRGFTDSLRCELLHDGSPVSVTMVQP 189

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779   7 ERWRDRLALVTGASGGIGAAVARALVQQGLKVV---------GCART--------------------------------- 44
Cdd:PRK05565    1 MKLMGKVAIVTGASGGIGRAIAELLAKEGAKVViaydineeaAQELLeeikeeggdaiavkadvsseedvenlveqivek 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  45 -------VGN--------------------IEVNVLALSICTREAYQSMKERNvdDGHIININSMSG-----HRVLplsv 92
Cdd:PRK05565   81 fgkidilVNNagisnfglvtdmtdeewdrvIDVNLTGVMLLTRYALPYMIKRK--SGVIVNISSIWGligasCEVL---- 154

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 2217313779  93 thfYSATKYAVTALTEGLRQELreAQTHIRATCLKP 128
Cdd:PRK05565  155 ---YSASKGAVNAFTKALAKEL--APSGIRVNAVAP 185

3-ketodihydrosphingosine reductase (KDSR) and related proteins, classical (c) SDR; These proteins include members identified as KDSR, ribitol type dehydrogenase, and others. The group shows strong conservation of the active site tetrad and glycine rich NAD-binding motif of the classical SDRs. 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 2217313779  11 DRLALVTGASGGIGAAVARALVQQGLKVVGCARTVG-------------------------------------------- 46
Cdd:cd08939     1 GKHVLITGGSSGIGKALAKELVKEGANVIIVARSESkleeaveeieaeanasgqkvsyisadlsdyeeveqafaqavekg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  47 ----------------------------NIEVNVLALSICTREAYQSMKERNvdDGHIININSMSGhrVLPLSVTHFYSA 98
Cdd:cd08939    81 gppdlvvncagisipglfedltaeeferGMDVNYFGSLNVAHAVLPLMKEQR--PGHIVFVSSQAA--LVGIYGYSAYCP 156

                         170       180       190
                  ....*....|....*....|....*....|....
gi 2217313779  99 TKYAVTALTEGLRQELREAQTHIraTCLKPEDVA 132
Cdd:cd08939   157 SKFALRGLAESLRQELKPYNIRV--SVVYPPDTD 188

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  11 DRLALVTGASGGIGAAVARALVQQGLKVV-GCART--------------------------------------------- 44
Cdd:PRK05557    5 GKVALVTGASRGIGRAIAERLAAQGANVViNYASSeagaealvaeigalggkalavqgdvsdaesveravdeakaefggv 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  45 ---VGN--------------------IEVNVLALSICTREAYQSMKERNvdDGHIININSMSGHRVLPlSVTHfYSATKY 101
Cdd:PRK05557   85 dilVNNagitrdnllmrmkeedwdrvIDTNLTGVFNLTKAVARPMMKQR--SGRIINISSVVGLMGNP-GQAN-YAASKA 160

                         170
                  ....*....|....
gi 2217313779 102 AVTALTEGLRQELR 115
Cdd:PRK05557  161 GVIGFTKSLARELA 174

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
                  ....*....|....*....|....*....|....*....
gi 2217313779  11 DRLALVTGASGGIGAAVARALVQQGLKVVGCARTVGNIE 49
Cdd:cd05344     1 GKVALVTAASSGIGLAIARALAREGARVAICARNRENLE 39

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  48 IEVN-VLALSICtrEAYQSM-KERNvdDGHIININSMSGHRVLPLSVThFYSATKYAVTALTEGLRQELreAQTHIRATC 125
Cdd:PRK08251  109 AETNfVAALAQC--EAAMEIfREQG--SGHLVLISSVSAVRGLPGVKA-AYAASKAGVASLGEGLRAEL--AKTPIKVST 181

                  ...
gi 2217313779 126 LKP 128
Cdd:PRK08251  182 IEP 184

classical (c) SDR, subgroup 7; These proteins are members of the classical SDR family, with a canonical active site triad (and also an active site Asn) and a typical Gly-rich NAD-binding motif. 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 2217313779  10 RDRLALVTGASGGIGAAVARALVQQGL-KVVGCARTVGN----------------------------------------- 47
Cdd:cd05354     2 KDKTVLVTGANRGIGKAFVESLLAHGAkKVYAAVRDPGSaahlvakygdkvvplrldvtdpesikaaaaqakdvdvvinn 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217313779  48 ---------------------IEVNVLA-LSICTreAYQSMKERNvDDGHIININSMSGHRVLPLSVThfYSATKYAVTA 105
Cdd:cd05354    82 agvlkpatlleegalealkqeMDVNVFGlLRLAQ--AFAPVLKAN-GGGAIVNLNSVASLKNFPAMGT--YSASKSAAYS 156

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 2217313779 106 LTEGLRQELREAQTHIRA-------TCL---------KPEDVAEAVI 136
Cdd:cd05354   157 LTQGLRAELAAQGTLVLSvhpgpidTRMaagaggpkeSPETVAEAVL 203