atypical (a) SDRs, subgroup 8; This subgroup contains atypical SDRs of unknown function. Proteins in this subgroup have a glycine-rich NAD(P)-binding motif consensus that resembles that of the extended SDRs, (GXXGXXG or GGXGXXG), but lacks the characteristic active site residues of the SDRs. A Cys often replaces the usual Lys of the YXXXK active site motif, while the upstream Ser is generally present and Arg replaces the usual Asn. 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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 552544637   3 WTSRKRARIIGSRVQMTEALQALVGRLDNKPACLINGSAIGWYGLRGDETLTEDANFEPAFVHEVCERWEQAAQKLERDG 82
Cdd:cd05242   74 WTEANKKEILSSRIESTRVLVEAIANAPAPPKVLISASAVGYYGHSGDEVLTENSPSGKDFLAEVCKAWEKAAQPASELG 153

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 552544637  83 VRVVLLRIGLVLGVEGGILAKLLTPFEFGGGGAMGSGRQWMSWIERDDLVRIIARAVADETLSGPVNATAPVPVRNAEFT 162
Cdd:cd05242  154 TRVVILRTGVVLGPDGGALPKMLLPFRLGLGGPLGSGRQWMSWIHIDDLVRLIEFAIENPDLSGPVNAVAPNPVTNAEFT 233

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 552544637 163 RALAKALHRPAFLRLPAWLLSTALGDMGRETMLAGQRVVPAKLVAAGFRFRHPELAPMLQVIT 225
Cdd:cd05242  234 KALGRALHRPAGLPVPAFALKLGFGEMRAELLLKGQRVLPERLLDAGFQFRYPDLEEALEELL 296

Domain of unknown function (DUF1731); This domain of unknown function appears towards the C-terminus of proteins of the NAD dependent epimerase/dehydratase family (pfam01370) in bacteria, eukaryotes and archaea. Many of the proteins in which it is found are involved in cell-division inhibition.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 552544637  177 LPAWLLSTALGDMGrETMLAGQRVVPAKLVAAGFRFRHPELAPMLQ 222
Cdd:pfam08338   1 VPAFALRLLLGEMA-ELLLEGQRVLPKRLLEAGFQFRYPDLEEALR 45

atypical (a) SDRs, subgroup 8; This subgroup contains atypical SDRs of unknown function. Proteins in this subgroup have a glycine-rich NAD(P)-binding motif consensus that resembles that of the extended SDRs, (GXXGXXG or GGXGXXG), but lacks the characteristic active site residues of the SDRs. A Cys often replaces the usual Lys of the YXXXK active site motif, while the upstream Ser is generally present and Arg replaces the usual Asn. 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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 552544637   3 WTSRKRARIIGSRVQMTEALQALVGRLDNKPACLINGSAIGWYGLRGDETLTEDANFEPAFVHEVCERWEQAAQKLERDG 82
Cdd:cd05242   74 WTEANKKEILSSRIESTRVLVEAIANAPAPPKVLISASAVGYYGHSGDEVLTENSPSGKDFLAEVCKAWEKAAQPASELG 153

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 552544637  83 VRVVLLRIGLVLGVEGGILAKLLTPFEFGGGGAMGSGRQWMSWIERDDLVRIIARAVADETLSGPVNATAPVPVRNAEFT 162
Cdd:cd05242  154 TRVVILRTGVVLGPDGGALPKMLLPFRLGLGGPLGSGRQWMSWIHIDDLVRLIEFAIENPDLSGPVNAVAPNPVTNAEFT 233

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 552544637 163 RALAKALHRPAFLRLPAWLLSTALGDMGRETMLAGQRVVPAKLVAAGFRFRHPELAPMLQVIT 225
Cdd:cd05242  234 KALGRALHRPAGLPVPAFALKLGFGEMRAELLLKGQRVLPERLLDAGFQFRYPDLEEALEELL 296

Domain of unknown function (DUF1731); This domain of unknown function appears towards the C-terminus of proteins of the NAD dependent epimerase/dehydratase family (pfam01370) in bacteria, eukaryotes and archaea. Many of the proteins in which it is found are involved in cell-division inhibition.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 552544637  177 LPAWLLSTALGDMGrETMLAGQRVVPAKLVAAGFRFRHPELAPMLQ 222
Cdd:pfam08338   1 VPAFALRLLLGEMA-ELLLEGQRVLPKRLLEAGFQFRYPDLEEALR 45

atypical (a) SDRs, subgroup 4; Atypical SDRs in this subgroup are poorly defined, one member is identified as a putative NAD-dependent epimerase/dehydratase. Atypical SDRs are distinct from classical SDRs. Members of this subgroup have a glycine-rich NAD(P)-binding motif that is related to, but is different from, the archetypical SDRs, GXGXXG. This subgroup also lacks most of the characteristic active site residues of the SDRs; however, the upstream Ser is present at the usual place, and some potential catalytic residues are present in place of the usual YXXXK active site motif. 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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 552544637 120 RQWMSWIERDDLVRIIARAVADETLSGPVNATAPVPVRNAEFTRALAKALHRPAflrlPAWllstalgdMGRETMLAGQR 199
Cdd:cd05266  174 NAPTNRIHVDDLVGALAFALQRPAPGPVYNVVDDLPVTRGEFYQAAAELLGLPP----PPF--------IPFAFLREGKR 241

                         90
                 ....*....|
gi 552544637 200 VVPAKLVAAG 209
Cdd:cd05266  242 VSNDRLKAEL 251