6-phosphogluconate dehydrogenase (decarboxylating) [Carbohydrate transport and metabolism];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1277923824   1 MLIAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDAMAQRVAESAAEADAL 50
Cdd:COG1023     1 MQIGMIGLGKMGGNMARRLLRHGHEVVGYDRNPEAVAALAAEGATGADSL 50

6-phosphogluconate dehydrogenase (decarboxylating) [Carbohydrate transport and metabolism];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1277923824   1 MLIAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDAMAQRVAESAAEADAL 50
Cdd:COG1023     1 MQIGMIGLGKMGGNMARRLLRHGHEVVGYDRNPEAVAALAAEGATGADSL 50

NAD binding domain of 6-phosphogluconate dehydrogenase; The NAD binding domain of 6-phosphogluconate dehydrogenase adopts a Rossmann fold.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1277923824   3 IAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDAMAQRVAESA 44
Cdd:pfam03446   2 IGFIGLGVMGSPMALNLLKAGYTVTVYNRTPEKVEELVAAGA 43

NAD(P) binding domain of leucine dehydrogenase, phenylalanine dehydrogenase, and valine dehydrogenase; Amino acid dehydrogenase (DH) is a widely distributed family of enzymes that catalyzes the oxidative deamination of an amino acid to its keto acid and ammonia with concomitant reduction of NADP+. For example, leucine DH catalyzes the reversible oxidative deamination of L-leucine and several other straight or branched chain amino acids to the corresponding 2-oxoacid derivative. Amino acid DH -like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyze the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DH, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an alpha-beta-alpha configuration. NAD binding involves numerous hydrogen and van der Waals contacts.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1277923824   3 IAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDAMAQRVAESAAEA 47
Cdd:cd01075    31 VAVQGLGKVGYKLAEHLLEEGAKLIVADINEEAVARAAELFGATV 75

6-phosphogluconate dehydrogenase (decarboxylating) [Carbohydrate transport and metabolism];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1277923824   1 MLIAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDAMAQRVAESAAEADAL 50
Cdd:COG1023     1 MQIGMIGLGKMGGNMARRLLRHGHEVVGYDRNPEAVAALAAEGATGADSL 50

3-hydroxyisobutyrate dehydrogenase or related beta-hydroxyacid dehydrogenase [Lipid transport and metabolism];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1277923824   1 MLIAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDAMAQ------RVAESAAEA 47
Cdd:COG2084     2 MKVGFIGLGAMGAPMARNLLKAGHEVTVWNRTPAKAEAlvaagaRVAASPAEA 54

6-phosphogluconate dehydrogenase (decarboxylating); This family resembles a larger family (gnd) of bacterial and eukaryotic 6-phosphogluconate dehydrogenases but differs from it by a deep split in a UPGMA similarity clustering tree and the lack of a central region of about 140 residues. Among complete genomes, it is found is found in Bacillus subtilis and Mycobacterium tuberculosis, both of which also contain gnd, and in Aquifex aeolicus. The protein from Methylobacillus flagellatus KT has been characterized as a decarboxylating 6-phosphogluconate dehydrogenase as part of an unusual formaldehyde oxidation cycle. In some sequenced organisms members of this family are the sole 6-phosphogluconate dehydrogenase present and are probably active in the pentose phosphate cycle. [Energy metabolism, Pentose phosphate pathway]

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1277923824   1 MLIAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDA 35
Cdd:TIGR00872   1 MQLGLIGLGRMGANIVRRLAKRGHDCVGYDHDQDA 35

sulfolactaldehyde 3-reductase;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1277923824   3 IAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDAMaQRVAESAAEADA 49
Cdd:PRK15461    4 IAFIGLGQMGSPMASNLLKQGHQLQVFDVNPQAV-DALVDKGATPAA 49

Trk system potassium transporter TrkA;

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1277923824   1 MLIAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDA 35
Cdd:PRK09496    1 MKIIIVGAGQVGYTLAENLSGENNDVTVIDTDEER 35

NAD(P) binding domain of leucine dehydrogenase, phenylalanine dehydrogenase, and valine dehydrogenase; Amino acid dehydrogenase (DH) is a widely distributed family of enzymes that catalyzes the oxidative deamination of an amino acid to its keto acid and ammonia with concomitant reduction of NADP+. For example, leucine DH catalyzes the reversible oxidative deamination of L-leucine and several other straight or branched chain amino acids to the corresponding 2-oxoacid derivative. Amino acid DH -like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyze the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DH, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an alpha-beta-alpha configuration. NAD binding involves numerous hydrogen and van der Waals contacts.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1277923824   3 IAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDAMAQRVAESAAEA 47
Cdd:cd01075    31 VAVQGLGKVGYKLAEHLLEEGAKLIVADINEEAVARAAELFGATV 75

3-hydroxyacyl-CoA dehydrogenase [Lipid transport and metabolism]; 3-hydroxyacyl-CoA dehydrogenase is part of the Pathway/BioSystem: Fatty acid biosynthesis

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1277923824   3 IAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDAMA---QRVAE-----------SAAEADALFAR 53
Cdd:COG1250     5 VAVIGAGTMGAGIAAVFANAGYEVVLLDISPEALErarARIAKlldklvkkgklTEEEADAALAR 69

putative NADPH-dependent glutamate synthase small subunit; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1277923824   3 IAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDA---MAQ-----RVAESAAEAD 48
Cdd:PRK12814  196 VAIIGAGPAGLTAAYYLLRKGHDVTIFDANEQAggmMRYgiprfRLPESVIDAD 249

extended (e) SDRs; Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1277923824   7 GLGRMGAHMARRLLRDGHDCVVYDqNPDA----MAQ-RVAESAAEADALFARN 54
Cdd:cd08946     6 GAGFIGSHLVRRLLERGHEVVVID-RLDVvvhlAALvGVPASWDNPDEDFETN 57

Prephenate dehydrogenase [Amino acid transport and metabolism]; Prephenate dehydrogenase is part of the Pathway/BioSystem: Aromatic amino acid biosynthesis

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1277923824   3 IAMVGLGRMGAHMARRLLRDG--HDCVVYDQNPDAMAQ--------RVAESAAEADA 49
Cdd:COG0287     4 IAIIGLGLIGGSLALALKRAGlaHEVVGVDRSPETLERalelgvidRAATDLEEAVA 60

atypical (a) SDRs, subgroup 3; These atypical SDR family members of unknown function have a glycine-rich NAD(P)-binding motif consensus that is very similar to the extended SDRs, GXXGXXG. Generally, this group has poor conservation of the active site tetrad, However, individual sequences do contain matches to the YXXXK active site motif, and generally Tyr or Asn in place of the upstream Ser found in most SDRs. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1277923824   1 MLIAMVGLGRMGAHMARRLLRDGHDCVVYDQNPDAMAQRVAESAAEADALFARN 54
Cdd:cd05229     1 TAHVLGASGPIGREVARELRRRGWDVRLVSRSGSKLAWLPGVEIVAADAMDASS 54

UDP-glucose 4 epimerase, subgroup 1, extended (e) SDRs; UDP-glucose 4 epimerase (aka UDP-galactose-4-epimerase), is a homodimeric extended SDR. It catalyzes the NAD-dependent conversion of UDP-galactose to UDP-glucose, the final step in Leloir galactose synthesis. This subgroup has the characteristic active site tetrad and NAD-binding motif of the extended SDRs. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they 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 numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, 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. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. 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.

                          10        20
                  ....*....|....*....|....
gi 1277923824   7 GLGRMGAHMARRLLRDGHDCVVYD 30
Cdd:cd05247     7 GAGYIGSHTVVELLEAGYDVVVLD 30