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 1063732146  64 VITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNKNKDAQLKSFEADMSSFESIFTFknsLEQWLSDsalH 143
Cdd:cd05327     5 VITGANSGIGKETARELAKRGAHVIIACRNEEKGEEAAAEIKKETGNAKVEVIQLDLSSLASVRQF---AEEFLAR---F 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 144 PSIQVLVNNAGILATSSRPTIDGYDRMIATNYVGPFFLTKLLLPLLKNSNvPSRVVNVTSFTHHSAFIQKLDKDSVTGVC 223
Cdd:cd05327    79 PRLDILINNAGIMAPPRRLTKDGFELQFAVNYLGHFLLTNLLLPVLKASA-PSRIVNVSSIAHRAGPIDFNDLDLENNKE 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 224 FSTSNQYpcARiyeySKLCLLLFSYELHRQLRliddSSHVSVIAADPGFVKTNIMRELPcyitsMVFLGFKILGLL--QS 301
Cdd:cd05327   158 YSPYKAY--GQ----SKLANILFTRELARRLE----GTGVTVNALHPGVVRTELLRRNG-----SFFLLYKLLRPFlkKS 222

                         250
                  ....*....|....
gi 1063732146 302 PEDGAESIIDAALS 315
Cdd:cd05327   223 PEQGAQTALYAATS 236

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 1063732146  64 VITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNKNKDAQLKSFEADMSSFESIFTFknsLEQWLSDsalH 143
Cdd:cd05327     5 VITGANSGIGKETARELAKRGAHVIIACRNEEKGEEAAAEIKKETGNAKVEVIQLDLSSLASVRQF---AEEFLAR---F 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 144 PSIQVLVNNAGILATSSRPTIDGYDRMIATNYVGPFFLTKLLLPLLKNSNvPSRVVNVTSFTHHSAFIQKLDKDSVTGVC 223
Cdd:cd05327    79 PRLDILINNAGIMAPPRRLTKDGFELQFAVNYLGHFLLTNLLLPVLKASA-PSRIVNVSSIAHRAGPIDFNDLDLENNKE 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 224 FSTSNQYpcARiyeySKLCLLLFSYELHRQLRliddSSHVSVIAADPGFVKTNIMRELPcyitsMVFLGFKILGLL--QS 301
Cdd:cd05327   158 YSPYKAY--GQ----SKLANILFTRELARRLE----GTGVTVNALHPGVVRTELLRRNG-----SFFLLYKLLRPFlkKS 222

                         250
                  ....*....|....
gi 1063732146 302 PEDGAESIIDAALS 315
Cdd:cd05327   223 PEQGAQTALYAATS 236

Short-chain dehydrogenase [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146  59 SRPICVITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNKNKDAQLksFEADMSSFESIFTFKNSLEqwls 138
Cdd:COG0300     4 TGKTVLITGASSGIGRALARALAARGARVVLVARDAERLEALAAELRAAGARVEV--VALDVTDPDAVAALAEAVL---- 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 139 dsALHPSIQVLVNNAGILATSS--RPTIDGYDRMIATNYVGPF-----FltklllpllknsnVP-------SRVVNVTSf 204
Cdd:COG0300    78 --ARFGPIDVLVNNAGVGGGGPfeELDLEDLRRVFEVNVFGPVrltraL-------------LPlmrargrGRIVNVSS- 141

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 205 thhsafiqkldkdsVTGVcFSTSNQYP-CAriyeySKLCLLLFSYELHRQLRliddSSHVSVIAADPGFVKTNIMRElpc 283
Cdd:COG0300   142 --------------VAGL-RGLPGMAAyAA-----SKAALEGFSESLRAELA----PTGVRVTAVCPGPVDTPFTAR--- 194

                         250       260       270
                  ....*....|....*....|....*....|
gi 1063732146 284 yitsmvfLGFKILGLLQSPEDGAESIIDAA 313
Cdd:COG0300   195 -------AGAPAGRPLLSPEEVARAILRAL 217

3-oxoacyl-(acyl-carrier-protein) reductase; This model represents 3-oxoacyl-[ACP] reductase, also called 3-ketoacyl-acyl carrier protein reductase, an enzyme of fatty acid biosynthesis. [Fatty acid and phospholipid metabolism, Biosynthesis]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146  63 CVITGATSGLGKATAFALAEKGFYVVLVGRSS-QLLSETLKEIKNKNKDAQlkSFEADMSSFESIftfKNSLEQWLSDsa 141
Cdd:TIGR01830   1 ALVTGASRGIGRAIALKLAKEGAKVIITYRSSeEGAEEVVEELKALGVKAL--GVVLDVSDREDV---KAVVEEIEEE-- 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1063732146 142 lHPSIQVLVNNAGI----LATssRPTIDGYDRMIATNYVGPF 179
Cdd:TIGR01830  74 -LGTIDILVNNAGItrdnLLM--RMKEEDWDAVIDTNLTGVF 112

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 1063732146  64 VITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNKNKDAQLKSFEADMSSFESIFTFknsLEQWLSDsalH 143
Cdd:cd05327     5 VITGANSGIGKETARELAKRGAHVIIACRNEEKGEEAAAEIKKETGNAKVEVIQLDLSSLASVRQF---AEEFLAR---F 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 144 PSIQVLVNNAGILATSSRPTIDGYDRMIATNYVGPFFLTKLLLPLLKNSNvPSRVVNVTSFTHHSAFIQKLDKDSVTGVC 223
Cdd:cd05327    79 PRLDILINNAGIMAPPRRLTKDGFELQFAVNYLGHFLLTNLLLPVLKASA-PSRIVNVSSIAHRAGPIDFNDLDLENNKE 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 224 FSTSNQYpcARiyeySKLCLLLFSYELHRQLRliddSSHVSVIAADPGFVKTNIMRELPcyitsMVFLGFKILGLL--QS 301
Cdd:cd05327   158 YSPYKAY--GQ----SKLANILFTRELARRLE----GTGVTVNALHPGVVRTELLRRNG-----SFFLLYKLLRPFlkKS 222

                         250
                  ....*....|....
gi 1063732146 302 PEDGAESIIDAALS 315
Cdd:cd05327   223 PEQGAQTALYAATS 236

retinol dehydrogenases (retinol-DHs), classical (c) SDRs; Classical SDR-like subgroup containing retinol-DHs and related proteins. Retinol is processed by a medium chain alcohol dehydrogenase followed by retinol-DHs. 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. 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 1063732146  64 VITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNKNKDAQLKSFEADMSSFESIFTFknsLEQWLSDsalH 143
Cdd:cd09807     5 IITGANTGIGKETARELARRGARVIMACRDMAKCEEAAAEIRRDTLNHEVIVRHLDLASLKSIRAF---AAEFLAE---E 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 144 PSIQVLVNNAGILATSSRPTIDGYDRMIATNYVGPFFLTKLLLPLLKNSnVPSRVVNVTSFTHHSAFIQKLDKDSvtgvc 223
Cdd:cd09807    79 DRLDVLINNAGVMRCPYSKTEDGFEMQFGVNHLGHFLLTNLLLDLLKKS-APSRIVNVSSLAHKAGKINFDDLNS----- 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 224 fstSNQYPCARIYEYSKLCLLLFSYELHRQLRliddSSHVSVIAADPGFVKTNIMRelpcYITSMVFLGFKILGLL---- 299
Cdd:cd09807   153 ---EKSYNTGFAYCQSKLANVLFTRELARRLQ----GTGVTVNALHPGVVRTELGR----HTGIHHLFLSTLLNPLfwpf 221

                         250
                  ....*....|....*..
gi 1063732146 300 -QSPEDGAESIIDAALS 315
Cdd:cd09807   222 vKTPREGAQTSIYLALA 238

NADP-dependent 3-hydroxy acid dehydrogenase YdfG [Energy production and conversion]; NADP-dependent 3-hydroxy acid dehydrogenase YdfG is part of the Pathway/BioSystem: Pyrimidine degradation

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146  58 SSRPICVITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIknknkDAQLKSFEADMSSFESIFTFKNSLEqwl 137
Cdd:COG4221     3 DKGKVALITGASSGIGAATARALAAAGARVVLAARRAERLEALAAEL-----GGRALAVPLDVTDEAAVEAAVAAAV--- 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 138 sdsALHPSIQVLVNNAGILATSS--RPTIDGYDRMIATNYVGPFFLTKLLlpllknsnVPS-------RVVNVTSFTHHS 208
Cdd:COG4221    75 ---AEFGRLDVLVNNAGVALLGPleELDPEDWDRMIDVNVKGVLYVTRAA--------LPAmrargsgHIVNISSIAGLR 143

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 209 AfiqkldkdsvtgvcFSTSNQYpCAriyeySKLCLLLFSYELHRQLRliddSSHVSVIAADPGFVKTNIMRELPCYITSM 288
Cdd:COG4221   144 P--------------YPGGAVY-AA-----TKAAVRGLSESLRAELR----PTGIRVTVIEPGAVDTEFLDSVFDGDAEA 199

                         250       260
                  ....*....|....*....|....*
gi 1063732146 289 VFLGFKILGLLQsPEDGAESIIDAA 313
Cdd:COG4221   200 AAAVYEGLEPLT-PEDVAEAVLFAL 223

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146  64 VITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNKNKDAqlKSFEADMSSFESIftfKNSLEQWLsdsALH 143
Cdd:pfam00106   4 LVTGASSGIGRAIAKRLAKEGAKVVLVDRSEEKLEAVAKELGALGGKA--LFIQGDVTDRAQV---KALVEQAV---ERL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 144 PSIQVLVNNAGI--LATSSRPTIDGYDRMIATNYVGPFFLTKLLLPLLKNSNVpSRVVNVTsfthhsafiqkldkdSVTG 221
Cdd:pfam00106  76 GRLDILVNNAGItgLGPFSELSDEDWERVIDVNLTGVFNLTRAVLPAMIKGSG-GRIVNIS---------------SVAG 139

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063732146 222 VcfstsNQYPCARIYEYSKLCLLLFSYELHRQLRliddSSHVSVIAADPGFVKTNIMRELP 282
Cdd:pfam00106 140 L-----VPYPGGSAYSASKAAVIGFTRSLALELA----PHGIRVNAVAPGGVDTDMTKELR 191

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 1063732146  62 ICVITGATSGLGKATAFALAEKGFY-VVLVGRSSQLLSETLKEIKNKNKDAQLksFEADMSSFESIFTFKNSLEQwlsds 140
Cdd:cd05324     2 VALVTGANRGIGFEIVRQLAKSGPGtVILTARDVERGQAAVEKLRAEGLSVRF--HQLDVTDDASIEAAADFVEE----- 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 141 aLHPSIQVLVNNAGILATS---SRPTIDGYDRMIATNYVGPFFLTKLLLPLLKNSNVPsRVVNVTSFthhsafiqkldkd 217
Cdd:cd05324    75 -KYGGLDILVNNAGIAFKGfddSTPTREQARETMKTNFFGTVDVTQALLPLLKKSPAG-RIVNVSSG------------- 139

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 218 svTGVCFSTsnqypcariYEYSKLCLLLFSYELHRQLrlidDSSHVSVIAADPGFVKTNimrelpcyitsmvfLGFKILG 297
Cdd:cd05324   140 --LGSLTSA---------YGVSKAALNALTRILAKEL----KETGIKVNACCPGWVKTD--------------MGGGKAP 190

                         250
                  ....*....|....*..
gi 1063732146 298 LlqSPEDGAESIIDAAL 314
Cdd:cd05324   191 K--TPEEGAETPVYLAL 205

oxidoreductase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146  64 VITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNKNKDaqlksfEADMSSFESIFTFKnslEQWLsdsALH 143
Cdd:PRK06196   30 IVTGGYSGLGLETTRALAQAGAHVIVPARRPDVAREALAGIDGVEVV------MLDLADLESVRAFA---ERFL---DSG 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 144 PSIQVLVNNAGILATSSRPTIDGYDRMIATNYVGPFFLTKLLLPLLKNSNvPSRVVNVTSFTHHSAFIQKLDKDSVTGvc 223
Cdd:PRK06196   98 RRIDILINNAGVMACPETRVGDGWEAQFATNHLGHFALVNLLWPALAAGA-GARVVALSSAGHRRSPIRWDDPHFTRG-- 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 224 fstsnqYPCARIYEYSKLCLLLFSYELHRQLRliddSSHVSVIAADPGFVKTNIMRELPcyITSMVFLGF------KILG 297
Cdd:PRK06196  175 ------YDKWLAYGQSKTANALFAVHLDKLGK----DQGVRAFSVHPGGILTPLQRHLP--REEQVALGWvdehgnPIDP 242

                         250
                  ....*....|....*...
gi 1063732146 298 LLQSPEDGAESIIDAALS 315
Cdd:PRK06196  243 GFKTPAQGAATQVWAATS 260

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 1063732146  62 ICVITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNKNKDAqlKSFEADMSSFESIftfKNSLEQWLSDsa 141
Cdd:cd05333     2 VALVTGASRGIGRAIALRLAAEGAKVAVTDRSEEAAAETVEEIKALGGNA--AALEADVSDREAV---EALVEKVEAE-- 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1063732146 142 lHPSIQVLVNNAGIL--ATSSRPTIDGYDRMIATNYVGPF 179
Cdd:cd05333    75 -FGPVDILVNNAGITrdNLLMRMSEEDWDAVINVNLTGVF 113

SDR family oxidoreductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146  62 ICVITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNKNKDAQlkSFEADMSSFESIFTFknsLEQWLSDsa 141
Cdd:PRK07201  373 VVLITGASSGIGRATAIKVAEAGATVFLVARNGEALDELVAEIRAKGGTAH--AYTCDLTDSAAVDHT---VKDILAE-- 445

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1063732146 142 lHPSIQVLVNNAG--IlatsSRPTIDGYDRM------IATNYVGP 178
Cdd:PRK07201  446 -HGHVDYLVNNAGrsI----RRSVENSTDRFhdyertMAVNYFGA 485

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 1063732146  65 ITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNknkdaqLKSFEADMSSFESIftfkNSLEQWLSDSalHP 144
Cdd:COG3967    10 ITGGTSGIGLALAKRLHARGNTVIITGRREEKLEEAAAANPG------LHTIVLDVADPASI----AALAEQVTAE--FP 77

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1063732146 145 SIQVLVNNAGIL----ATSSRPTIDGYDRMIATNYVGP 178
Cdd:COG3967    78 DLNVLINNAGIMraedLLDEAEDLADAEREITTNLLGP 115

Light-dependent NADPH-protochlorophyllide oxidoreductase [Coenzyme transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146  58 SSRPICVITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNKNKDAQLksFEADMSSFESIFTFKNSLEqwl 137
Cdd:COG5748     4 DQKSTVIITGASSGVGLYAAKALADRGWHVIMACRDLEKAEAAAQELGIPPDSYTI--IHIDLASLESVRRFVADFR--- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 138 sdsALHPSIQVLVNNAGI---LATSSRPTIDGYDRMIATNYVGPFFLTKLLLPLLKNSNVPS-RVVNVTSFTHHSA---- 209
Cdd:COG5748    79 ---ALGRPLDALVCNAAVyypLLKEPLRSPDGYELSVATNHLGHFLLCNLLLEDLKKSPASDpRLVILGTVTANPKelgg 155

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063732146 210 ---FIQKLDKDSVTGvcFSTSNQYPCARI----------YEYSKLCLLLFSYELHRQLRlidDSSHVSVIAADPGFVKT 275
Cdd:COG5748   156 kipIPAPPDLGDLEG--FEAGFKAPISMIdgkkfkpgkaYKDSKLCNVLTMRELHRRYH---ESTGIVFSSLYPGCVAD 229

3-oxoacyl-ACP reductase FabG;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146  64 VITGATSGLGKATAFALAEKGFYVVLVGRSSQLLSETLKEIKNKNKDAQLksFEADMSSFESiftFKNSLEQwlsDSALH 143
Cdd:PRK05653    9 LVTGASRGIGRAIALRLAADGAKVVIYDSNEEAAEALAAELRAAGGEARV--LVFDVSDEAA---VRALIEA---AVEAF 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1063732146 144 PSIQVLVNNAGIlaTSSRPTIDG----YDRMIATN 174
Cdd:PRK05653   81 GALDILVNNAGI--TRDALLPRMseedWDRVIDVN 113

insect type alcohol dehydrogenase (ADH)-like, classical (c) SDRs; This subgroup contains insect type ADH, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) type I; these proteins are classical SDRs. ADH catalyzes the NAD+-dependent oxidation of alcohols to aldehydes/ketones. This subgroup is distinct from the zinc-dependent alcohol dehydrogenases of the medium chain dehydrogenase/reductase family, and evolved in fruit flies to allow the digestion of fermenting fruit. 15-PGDH catalyzes the NAD-dependent interconversion of (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate and (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate, and has a typical SDR glycine-rich NAD-binding motif, which is not fully present in ADH. 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 1063732146  64 VITGATSGLGKATAFALAEKGFYVVLVGRSSQLlsETLKEIKNKNKDAQLKSFEADMSSFESIFT-FKNSLEQwlsdsal 142
Cdd:cd05323     4 IITGGASGIGLATAKLLLKKGAKVAILDRNENP--GAAAELQAINPKVKATFVQCDVTSWEQLAAaFKKAIEK------- 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 143 HPSIQVLVNNAGILATSS----RPTIDGYDRMIATNYVGpffltklllpllknsnvpsrVVNVTsfthhSAFIQKLDKD- 217
Cdd:cd05323    75 FGRVDILINNAGILDEKSylfaGKLPPPWEKTIDVNLTG--------------------VINTT-----YLALHYMDKNk 129

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063732146 218 -----------SVTGVcfstsnqYPCAR--IYEYSKLCLLLFSyelhRQLRLIDDSSH-VSVIAADPGFVKTNIMRELpc 283
Cdd:cd05323   130 ggkggvivnigSVAGL-------YPAPQfpVYSASKHGVVGFT----RSLADLLEYKTgVRVNAICPGFTNTPLLPDL-- 196

                         250       260       270
                  ....*....|....*....|....*....|
gi 1063732146 284 yiTSMVFLGFKILGlLQSPEDGAESIIDAA 313
Cdd:cd05323   197 --VAKEAEMLPSAP-TQSPEVVAKAIVYLI 223

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 1063732146  64 VITGATSGLGKATAFALAEKGFYVVLVGRSSQLLsETLKEIKNKNkdaqLKSFEADMSSFESIftfKNSLEQWLsdsALH 143
Cdd:cd05374     4 LITGCSSGIGLALALALAAQGYRVIATARNPDKL-ESLGELLNDN----LEVLELDVTDEESI---KAAVKEVI---ERF 72

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1063732146 144 PSIQVLVNNAGILATSsrP----TIDGYDRMIATNYVGP 178
Cdd:cd05374    73 GRIDVLVNNAGYGLFG--PleetSIEEVRELFEVNVFGP 109

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 1063732146  60 RPICVITGATSGLGKATAFALAEKGFYVVLV-GRSSQLLSETLKEIKNKNKDAQlkSFEADMSSFesiftfknSLEQWLS 138
Cdd:cd05337     1 RPVAIVTGASRGIGRAIATELAARGFDIAINdLPDDDQATEVVAEVLAAGRRAI--YFQADIGEL--------SDHEALL 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1063732146 139 DSALHP--SIQVLVNNAGIlatSSRP-------TIDGYDRMIATNYVGPFF 180
Cdd:cd05337    71 DQAWEDfgRLDCLVNNAGI---AVRPrgdlldlTEDSFDRLIAINLRGPFF 118