13-PGR is a bifunctional enzyme with delta-13 15-prostaglandin reductase and leukotriene B4 12 hydroxydehydrogenase activity; Prostaglandins and related eicosanoids are metabolized by the oxidation of the 15(S)-hydroxyl group of the NAD+-dependent (type I 15-PGDH) 15-prostaglandin dehydrogenase (15-PGDH) followed by reduction by NADPH/NADH-dependent (type II 15-PGDH) delta-13 15-prostaglandin reductase (13-PGR) to 15-keto- 13,14,-dihydroprostaglandins. 13-PGR is a bifunctional enzyme, since it also has leukotriene B(4) 12-hydroxydehydrogenase activity. These 15-PGDH and related enzymes are members of the medium chain dehydrogenase/reductase family. The medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH. MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR). The MDR proteins have 2 domains: a C-terminal NAD(P) binding-Rossmann fold domain of a beta-alpha form and an N-terminal catalytic domain with distant homology to GroES.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731   2 VQAKSWTLKKHFEGFPTDGNFELKTTELPPLNNGEVLLEALFLSVDPYMRVAAKKLKEGDRMMGEQVARVVESKNSAFPK 81
Cdd:cd08294    1 VKAKTWVLKKHFDGKPKESDFELVEEELPPLKDGEVLCEALFLSVDPYMRPYSKRLNEGDTMIGTQVAKVIESKNSKFPV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  82 GTIVAALLGWTSHSISDG---NGLTKLPVEWPDKLPLSLALGTVGMPGLTAYFGLLDICGVKGGETVMVSAAAGAVGSVV 158
Cdd:cd08294   81 GTIVVASFGWRTHTVSDGkdqPDLYKLPADLPDDLPPSLALGVLGMPGLTAYFGLLEICKPKAGETVVVNGAAGAVGSLV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 159 GQIAKLKGCKVVGTAGSDEKVAYLKKLGFDVAFNYKTVkSLEEALRTASPDGYDCYFDNVGGEFSNAVILQMKTFGRIAI 238
Cdd:cd08294  161 GQIAKIKGCKVIGCAGSDDKVAWLKELGFDAVFNYKTV-SLEEALKEAAPDGIDCYFDNVGGEFSSTVLSHMNDFGRVAV 239

                        250       260       270
                 ....*....|....*....|....*....|.
gi 755506731 239 CGAISQYNRT----GPCPQGTLLLQMPSPRG 265
Cdd:cd08294  240 CGSISTYNDKepkkGPYVQETIIFKQLKMEG 270

putative allyl alcohol dehydrogenase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731   2 VQAKSWTLKKHFEGFPTDGNFELK---TTEL-PPLNNGEVLLEALFLSVDPYMRVAAKKLKE--------GDRMMGEQVA 69
Cdd:PLN03154   7 VENKQVILKNYIDGIPKETDMEVKlgnKIELkAPKGSGAFLVKNLYLSCDPYMRGRMRDFHDsylppfvpGQRIEGFGVS 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  70 RVVESKNSAFPKGTIVAALLGWTSHSISDGNGLTKLPVEWPDKLPLSLALGTVGMPGLTAYFGLLDICGVKGGETVMVSA 149
Cdd:PLN03154  87 KVVDSDDPNFKPGDLISGITGWEEYSLIRSSDNQLRKIQLQDDIPLSYHLGLLGMAGFTAYAGFYEVCSPKKGDSVFVSA 166

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 150 AAGAVGSVVGQIAKLKGCKVVGTAGSDEKVAYLK-KLGFDVAFNYKTVKSLEEALRTASPDGYDCYFDNVGGEFSNAVIL 228
Cdd:PLN03154 167 ASGAVGQLVGQLAKLHGCYVVGSAGSSQKVDLLKnKLGFDEAFNYKEEPDLDAALKRYFPEGIDIYFDNVGGDMLDAALL 246

                        250
                 ....*....|....*.
gi 755506731 229 QMKTFGRIAICGAISQ 244
Cdd:PLN03154 247 NMKIHGRIAVCGMVSL 262

Enoylreductase; Enoylreductase in Polyketide synthases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731    85 VAALL--GWTSHSISDGNGLTKLPVEWpdklplSLALG-TVGMPGLTAYFGLLDICGVKGGETVMVSAAAGAVGSVVGQI 161
Cdd:smart00829  50 VMGLApgAFATRVVTDARLVVPIPDGW------SFEEAaTVPVVFLTAYYALVDLARLRPGESVLIHAAAGGVGQAAIQL 123

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 755506731   162 AKLKGCKVVGTAGSDEKVAYLKKLGFDVA--FNYKTVkSLEEALRTA 206
Cdd:smart00829 124 ARHLGAEVFATAGSPEKRDFLRALGIPDDhiFSSRDL-SFADEILRA 169

13-PGR is a bifunctional enzyme with delta-13 15-prostaglandin reductase and leukotriene B4 12 hydroxydehydrogenase activity; Prostaglandins and related eicosanoids are metabolized by the oxidation of the 15(S)-hydroxyl group of the NAD+-dependent (type I 15-PGDH) 15-prostaglandin dehydrogenase (15-PGDH) followed by reduction by NADPH/NADH-dependent (type II 15-PGDH) delta-13 15-prostaglandin reductase (13-PGR) to 15-keto- 13,14,-dihydroprostaglandins. 13-PGR is a bifunctional enzyme, since it also has leukotriene B(4) 12-hydroxydehydrogenase activity. These 15-PGDH and related enzymes are members of the medium chain dehydrogenase/reductase family. The medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH. MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR). The MDR proteins have 2 domains: a C-terminal NAD(P) binding-Rossmann fold domain of a beta-alpha form and an N-terminal catalytic domain with distant homology to GroES.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731   2 VQAKSWTLKKHFEGFPTDGNFELKTTELPPLNNGEVLLEALFLSVDPYMRVAAKKLKEGDRMMGEQVARVVESKNSAFPK 81
Cdd:cd08294    1 VKAKTWVLKKHFDGKPKESDFELVEEELPPLKDGEVLCEALFLSVDPYMRPYSKRLNEGDTMIGTQVAKVIESKNSKFPV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  82 GTIVAALLGWTSHSISDG---NGLTKLPVEWPDKLPLSLALGTVGMPGLTAYFGLLDICGVKGGETVMVSAAAGAVGSVV 158
Cdd:cd08294   81 GTIVVASFGWRTHTVSDGkdqPDLYKLPADLPDDLPPSLALGVLGMPGLTAYFGLLEICKPKAGETVVVNGAAGAVGSLV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 159 GQIAKLKGCKVVGTAGSDEKVAYLKKLGFDVAFNYKTVkSLEEALRTASPDGYDCYFDNVGGEFSNAVILQMKTFGRIAI 238
Cdd:cd08294  161 GQIAKIKGCKVIGCAGSDDKVAWLKELGFDAVFNYKTV-SLEEALKEAAPDGIDCYFDNVGGEFSSTVLSHMNDFGRVAV 239

                        250       260       270
                 ....*....|....*....|....*....|.
gi 755506731 239 CGAISQYNRT----GPCPQGTLLLQMPSPRG 265
Cdd:cd08294  240 CGSISTYNDKepkkGPYVQETIIFKQLKMEG 270

Prostaglandin dehydrogenases; Prostaglandins and related eicosanoids are metabolized by the oxidation of the 15(S)-hydroxyl group of the NAD+-dependent (type I 15-PGDH) 15-prostaglandin dehydrogenase (15-PGDH) followed by reduction by NADPH/NADH-dependent (type II 15-PGDH) delta-13 15-prostaglandin reductase (13-PGR) to 15-keto-13,14,-dihydroprostaglandins. 13-PGR is a bifunctional enzyme, since it also has leukotriene B(4) 12-hydroxydehydrogenase activity. These 15-PGDH and related enzymes are members of the medium chain dehydrogenase/reductase family. The medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH. MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR). The MDR proteins have 2 domains: a C-terminal NAD(P) binding-Rossmann fold domain of a beta-alpha form and an N-terminal catalytic domain with distant homology to GroES.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731   3 QAKSWTLKKHFEGFPTDGNFELKTTELPPLNNGEVLLEALFLSVDPYMRV-------AAKKLKEGDRMMGEQVARVVESK 75
Cdd:cd05288    1 SNRQVVLAKRPEGPPPPDDFELVEVPLPELKDGEVLVRTLYLSVDPYMRGwmsdaksYSPPVQLGEPMRGGGVGEVVESR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  76 NSAFPKGTIVAALLGWTSHSISDGN-GLTKLPVEWPdkLPLSLALGTVGMPGLTAYFGLLDICGVKGGETVMVSAAAGAV 154
Cdd:cd05288   81 SPDFKVGDLVSGFLGWQEYAVVDGAsGLRKLDPSLG--LPLSAYLGVLGMTGLTAYFGLTEIGKPKPGETVVVSAAAGAV 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 155 GSVVGQIAKLKGCKVVGTAGSDEKVAYLKK-LGFDVAFNYKTVkSLEEALRTASPDGYDCYFDNVGGEFSNAVILQMKTF 233
Cdd:cd05288  159 GSVVGQIAKLLGARVVGIAGSDEKCRWLVEeLGFDAAINYKTP-DLAEALKEAAPDGIDVYFDNVGGEILDAALTLLNKG 237

                        250
                 ....*....|....*..
gi 755506731 234 GRIAICGAISQYNRTGP 250
Cdd:cd05288  238 GRIALCGAISQYNATEP 254

Prostaglandin reductase; Prostaglandins and related eicosanoids are metabolized by the oxidation of the 15(S)-hydroxyl group of the NAD+-dependent (type I 15-PGDH) 15-prostaglandin dehydrogenase (15-PGDH) followed by reduction by NADPH/NADH-dependent (type II 15-PGDH) delta-13 15-prostaglandin reductase (13-PGR) to 15-keto-13,14,-dihydroprostaglandins. 13-PGR is a bifunctional enzyme, since it also has leukotriene B(4) 12-hydroxydehydrogenase activity. These 15-PGDH and related enzymes are members of the medium chain dehydrogenase/reductase family. The medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH. MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR). The MDR proteins have 2 domains: a C-terminal NAD(P) binding-Rossmann fold domain of a beta-alpha form and an N-terminal catalytic domain with distant homology to GroES.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  15 GFPTDGNFELKTTELPP-LNNGEVLLEALFLSVDPYMR-----------VAAKKLKEGdrMMGEQVARVVESKNSAFPKG 82
Cdd:cd08293   16 GNPVAENFRVEECTLPDeLNEGQVLVRTLYLSVDPYMRcrmnedtgtdyLAPWQLSQV--LDGGGVGVVEESKHQKFAVG 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  83 TIVAAL-LGWTSHSISDGNGLTKLPVEWPDKLPlSLALGTVGMPGLTAYFGLLDICGVKGG--ETVMVSAAAGAVGSVVG 159
Cdd:cd08293   94 DIVTSFnWPWQTYAVLDGSSLEKVDPQLVDGHL-SYFLGAVGLPGLTALIGIQEKGHITPGanQTMVVSGAAGACGSLAG 172

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 160 QIAKLKGC-KVVGTAGSDEKVAYLKK-LGFDVAFNYKTvKSLEEALRTASPDGYDCYFDNVGGEFSNAVILQMKTFGRIA 237
Cdd:cd08293  173 QIGRLLGCsRVVGICGSDEKCQLLKSeLGFDAAINYKT-DNVAERLRELCPEGVDVYFDNVGGEISDTVISQMNENSHII 251

                        250
                 ....*....|....*
gi 755506731 238 ICGAISQYNRTGPCP 252
Cdd:cd08293  252 LCGQISQYNKDVPYP 266

N-terminal domain of oxidoreductase; N-terminal region of oxidoreductase and prostaglandin reductase and alcohol dehydrogenase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731    5 KSWTLKKHFEGFPTDGNFELKTTELPPLNNGEVLLEALFLSVDPYMRVAAKKLKE-------GDRMMGEQVARVVESKNS 77
Cdd:pfam16884   1 KQWLLAKRPEGVPTPSDFELVEAELPELGDGEVLVRTLYLSVDPYMRGRMNDAKSyvppvelGDVMRGGAVGEVVESNNP 80

                          90       100
                  ....*....|....*....|....*...
gi 755506731   78 AFPKGTIVAALLGWTSHSISDGNGLTKL 105
Cdd:pfam16884  81 DFPVGDLVLGMLGWQDYAVSDGKGLTKV 108

Mgc45594 gene product and other MDR family members; Includes Human Mgc45594 gene product of undetermined function. The medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH. MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR). The MDR proteins have 2 domains: a C-terminal NAD(P) binding-Rossmann fold domain of a beta-alpha form and an N-terminal catalytic domain with distant homology to GroES.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 104 KLPVEWPDKLPLSLAlgtvgmpGLTAYFGLLDICGVKGGETVMVSAAAGAVGSVVGQIAKLKGCKVVGTAGSDEKVAYLK 183
Cdd:cd08250  109 PVPELKPEVLPLLVS-------GLTASIALEEVGEMKSGETVLVTAAAGGTGQFAVQLAKLAGCHVIGTCSSDEKAEFLK 181

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 755506731 184 KLGFDVAFNYKTvKSLEEALRTASPDGYDCYFDNVGGEFSNAVILQMKTFGRIAICGAISQY-NRTGPCPQGTLLLQM 260
Cdd:cd08250  182 SLGCDRPINYKT-EDLGEVLKKEYPKGVDVVYESVGGEMFDTCVDNLALKGRLIVIGFISGYqSGTGPSPVKGATLPP 258

Quinone oxidoreductase (QOR); QOR catalyzes the conversion of a quinone + NAD(P)H to a hydroquinone + NAD(P)+. Quinones are cyclic diones derived from aromatic compounds. Membrane bound QOR acts in the respiratory chains of bacteria and mitochondria, while soluble QOR acts to protect from toxic quinones (e.g. DT-diaphorase) or as a soluble eye-lens protein in some vertebrates (e.g. zeta-crystalin). QOR reduces quinones through a semi-quinone intermediate via a NAD(P)H-dependent single electron transfer. QOR is a member of the medium chain dehydrogenase/reductase family, but lacks the zinc-binding sites of the prototypical alcohol dehydrogenases of this group. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which has a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. A GxGxxG motif after the first mononucleotide contact half allows the close contact of the coenzyme with the ADH backbone. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site, and a structural zinc in a lobe of the catalytic domain. NAD(H)-binding occurs in the cleft between the catalytic and coenzyme-binding domains at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding. In human ADH catalysis, the zinc ion helps coordinate the alcohol, followed by deprotonation of a histidine, the ribose of NAD, a serine, then the alcohol, which allows the transfer of a hydride to NAD+, creating NADH and a zinc-bound aldehyde or ketone. In yeast and some bacteria, the active site zinc binds an aldehyde, polarizing it, and leading to the reverse reaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  65 GEQVARVVES---KNSAFPKGTIVAALLGW---TSHSISDGNGLTKLPvewpDKLPLSLALGtVGMPGLTAYFGLLDICG 138
Cdd:cd08241   62 GSEVAGVVEAvgeGVTGFKVGDRVVALTGQggfAEEVVVPAAAVFPLP----DGLSFEEAAA-LPVTYGTAYHALVRRAR 136

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 139 VKGGETVMVSAAAGAVGSVVGQIAKLKGCKVVGTAGSDEKVAYLKKLGFDVAFNYKTvKSLEEALRTA-SPDGYDCYFDN 217
Cdd:cd08241  137 LQPGETVLVLGAAGGVGLAAVQLAKALGARVIAAASSEEKLALARALGADHVIDYRD-PDLRERVKALtGGRGVDVVYDP 215

                        170
                 ....*....|....*....
gi 755506731 218 VGGEFSNAVILQMKTFGRI 236
Cdd:cd08241  216 VGGDVFEASLRSLAWGGRL 234

PIG3 p53-inducible quinone oxidoreductase; PIG3 p53-inducible quinone oxidoreductase, a medium chain dehydrogenase/reductase family member, acts in the apoptotic pathway. PIG3 reduces ortho-quinones, but its apoptotic activity has been attributed to oxidative stress generation, since overexpression of PIG3 accumulates reactive oxygen species. PIG3 resembles the MDR family member quinone reductases, which catalyze the reduction of quinone to hydroxyquinone. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes or ketones. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which has a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. A GxGxxG motif after the first mononucleotide contact half allows the close contact of the coenzyme with the ADH backbone. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site, and a structural zinc in a lobe of the catalytic domain. NAD(H) binding occurs in the cleft between the catalytic and coenzyme-binding domains at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding. In human ADH catalysis, the zinc ion helps coordinate the alcohol, followed by deprotonation of a histidine, the ribose of NAD, a serine, then the alcohol, which allows the transfer of a hydride to NAD+, creating NADH and a zinc-bound aldehyde or ketone. In yeast and some bacteria, the active site zinc binds an aldehyde, polarizing it, and leading to the reverse reaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  12 HFEGFPTDGNFELKTTELPPLNNGEVLLealflsvdpymRVAAKKLKEGDRM---------------MGEQVARVVE--- 73
Cdd:cd05276    5 VIKEPGGPEVLELGEVPKPAPGPGEVLI-----------RVAAAGVNRADLLqrqglyppppgasdiLGLEVAGVVVavg 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  74 SKNSAFPKGTIVAALL---GWTSHSISDGNGLtkLPVewPDKLPLSLAlgtVGMP--GLTAYFGLLDICGVKGGETVMVS 148
Cdd:cd05276   74 PGVTGWKVGDRVCALLaggGYAEYVVVPAGQL--LPV--PEGLSLVEA---AALPevFFTAWQNLFQLGGLKAGETVLIH 146

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 149 AAAGAVGSVVGQIAKLKGCKVVGTAGSDEKVAYLKKLGFDVAFNYKTVKSLEEALRTASPDGYDCYFDNVGGEFSNAVIL 228
Cdd:cd05276  147 GGASGVGTAAIQLAKALGARVIATAGSEEKLEACRALGADVAINYRTEDFAEEVKEATGGRGVDVILDMVGGDYLARNLR 226

                        250
                 ....*....|..
gi 755506731 229 QMKTFGRIAICG 240
Cdd:cd05276  227 ALAPDGRLVLIG 238

alcohol dehydrogenase and quinone reductase-like medium chain degydrogenases/reductases; Members identified as zinc-dependent alcohol dehydrogenases and quinone oxidoreductase. QOR catalyzes the conversion of a quinone + NAD(P)H to a hydroquinone + NAD(P)+. Quinones are cyclic diones derived from aromatic compounds. Membrane bound QOR actin the respiratory chains of bacteria and mitochondria, while soluble QOR acts to protect from toxic quinones (e.g. DT-diaphorase) or as a soluble eye-lens protein in some vertebrates (e.g. zeta-crystalin). QOR reduces quinones through a semi-quinone intermediate via a NAD(P)H-dependent single electron transfer. QOR is a member of the medium chain dehydrogenase/reductase family, but lacks the zinc-binding sites of the prototypical alcohol dehydrogenases of this group. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which has a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. A GxGxxG motif after the first mononucleotide contact half allows the close contact of the coenzyme with the ADH backbone. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site and a structural zinc in a lobe of the catalytic domain. NAD(H) binding occurs in the cleft between the catalytic and coenzyme-binding domains at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding. In human ADH catalysis, the zinc ion helps coordinate the alcohol, followed by deprotonation of a histidine, the ribose of NAD, a serine, then the alcohol, which allows the transfer of a hydride to NAD+, creating NADH and a zinc-bound aldehyde or ketone. In yeast and some bacteria, the active site zinc binds an aldehyde, polarizing it, and leading to the reverse reaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 110 PDKLPLSLAlGTVGMPGLTAYFGLLDICGVKGGETVMVSAAAGAVGSVVGQIAKLKGCKVVGTAgSDEKVAYLKKLGFDV 189
Cdd:cd05289  114 PANLSFEEA-AALPLAGLTAWQALFELGGLKAGQTVLIHGAAGGVGSFAVQLAKARGARVIATA-SAANADFLRSLGADE 191

                         90       100       110
                 ....*....|....*....|....*....|..
gi 755506731 190 AFNYKTvkslEEALRTASPDGYDCYFDNVGGE 221
Cdd:cd05289  192 VIDYTK----GDFERAAAPGGVDAVLDTVGGE 219

Medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family; This group is a member of the medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family, but lacks the zinc-binding sites of the zinc-dependent alcohol dehydrogenases. The medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH. MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR). The MDR proteins have 2 domains: a C-terminal NAD(P)-binding Rossmann fold domain of a beta-alpha form and an N-terminal catalytic domain with distant homology to GroES. The MDR group contains a host of activities, including the founding alcohol dehydrogenase (ADH), quinone reductase, sorbitol dehydrogenase, formaldehyde dehydrogenase, butanediol DH, ketose reductase, cinnamyl reductase, and numerous others. The zinc-dependent alcohol dehydrogenases (ADHs) catalyze the NAD(P)(H)-dependent interconversion of alcohols to aldehydes or ketones. Active site zinc has a catalytic role, while structural zinc aids in stability. ADH-like proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and generally have 2 tightly bound zinc atoms per subunit. The active site zinc is coordinated by a histidine, two cysteines, and a water molecule. The second zinc seems to play a structural role, affects subunit interactions, and is typically coordinated by 4 cysteines.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  23 ELKTTELPPLNNGEVLLEALFLSV---DPYMRV----AAKKLKegdRMMGEQVARVVES---KNSAFPKGTIVAALL--- 89
Cdd:cd08275   15 KVEKEALPEPSSGEVRVRVEACGLnfaDLMARQglydSAPKPP---FVPGFECAGTVEAvgeGVKDFKVGDRVMGLTrfg 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  90 GWTSHSISDGNGLTKLPVEWpdklplSLALGtVGMP--GLTAYFGLLDICGVKGGETVMVSAAAGAVGSVVGQIAK-LKG 166
Cdd:cd08275   92 GYAEVVNVPADQVFPLPDGM------SFEEA-AAFPvnYLTAYYALFELGNLRPGQSVLVHSAAGGVGLAAGQLCKtVPN 164

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 755506731 167 CKVVGTAgSDEKVAYLKKLGFDVAFNYKTvKSLEEALRTASPDGYDCYFDNVGGEFSNAVILQMKTFGRIAICGA 241
Cdd:cd08275  165 VTVVGTA-SASKHEALKENGVTHVIDYRT-QDYVEEVKKISPEGVDIVLDALGGEDTRKSYDLLKPMGRLVVYGA 237

Quinone oxidoreductase (QOR); Quinone oxidoreductase (QOR) and 2-haloacrylate reductase. QOR catalyzes the conversion of a quinone + NAD(P)H to a hydroquinone + NAD(P)+. Quinones are cyclic diones derived from aromatic compounds. Membrane bound QOR actin the respiratory chains of bacteria and mitochondria, while soluble QOR acts to protect from toxic quinones (e.g. DT-diaphorase) or as a soluble eye-lens protein in some vertebrates (e.g. zeta-crystalin). QOR reduces quinones through a semi-quinone intermediate via a NAD(P)H-dependent single electron transfer. QOR is a member of the medium chain dehydrogenase/reductase family, but lacks the zinc-binding sites of the prototypical alcohol dehydrogenases of this group. 2-haloacrylate reductase, a member of this subgroup, catalyzes the NADPH-dependent reduction of a carbon-carbon double bond in organohalogen compounds. Although similar to QOR, Burkholderia 2-haloacrylate reductase does not act on the quinones 1,4-benzoquinone and 1,4-naphthoquinone. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which have a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. A GxGxxG motif after the first mononucleotide contact half allows the close contact of the coenzyme with the ADH backbone. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site and a structural zinc in a lobe of the catalytic domain. NAD(H) binding occurs in the cleft between the catalytic and coenzyme-binding domains at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding. In human ADH catalysis, the zinc ion helps coordinate the alcohol, followed by deprotonation of a histidine, the ribose of NAD, a serine, then the alcohol, which allows the transfer of a hydride to NAD+, creating NADH and a zinc-bound aldehyde or ketone. In yeast and some bacteria, the active site zinc binds an aldehyde, polarizing it, and leading to the reverse reaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  22 FELKTTELPPLNNGEVLLEALFLSV---DPYMR--VAAKKLKEGdrmMGEQVARVVE---SKNSAFPKGTIVAALLGWTS 93
Cdd:cd05286   14 LEYEDVPVPEPGPGEVLVRNTAIGVnfiDTYFRsgLYPLPLPFV---LGVEGAGVVEavgPGVTGFKVGDRVAYAGPPGA 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  94 HSisdgnGLTKLPVEWPDKLPLSLALGTVG---MPGLTAYFGLLDICGVKGGETVMVSAAAGAVGSVVGQIAKLKGCKVV 170
Cdd:cd05286   91 YA-----EYRVVPASRLVKLPDGISDETAAallLQGLTAHYLLRETYPVKPGDTVLVHAAAGGVGLLLTQWAKALGATVI 165

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 755506731 171 GTAGSDEKVAYLKKLGFDVAFNYKTVKSLEEALRTASPDGYDCYFDNVGG 220
Cdd:cd05286  166 GTVSSEEKAELARAAGADHVINYRDEDFVERVREITGGRGVDVVYDGVGK 215

Medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family; This group is a member of the medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family, but lacks the zinc-binding sites of the zinc-dependent alcohol dehydrogenases. The medium chain dehydrogenases/reductase (MDR)/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH. MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR). The MDR proteins have 2 domains: a C-terminal NAD(P)-binding Rossmann fold domain of a beta-alpha form and an N-terminal catalytic domain with distant homology to GroES. The MDR group contains a host of activities, including the founding alcohol dehydrogenase (ADH), quinone reductase, sorbitol dehydrogenase, formaldehyde dehydrogenase, butanediol DH, ketose reductase, cinnamyl reductase, and numerous others. The zinc-dependent alcohol dehydrogenases (ADHs) catalyze the NAD(P)(H)-dependent interconversion of alcohols to aldehydes or ketones. Active site zinc has a catalytic role, while structural zinc aids in stability. ADH-like proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and generally have 2 tightly bound zinc atoms per subunit. The active site zinc is coordinated by a histidine, two cysteines, and a water molecule. The second zinc seems to play a structural role, affects subunit interactions, and is typically coordinated by 4 cysteines.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 107 VEWPDKLPLSLAlGTVGMPGLTAYFGLLDICGVKGGETVMVSAAAGAVGSVVGQIAKLKGCKVVGTAGSDEKVAYLKKLG 186
Cdd:cd08268  111 VKLPDGLSFVEA-AALWMQYLTAYGALVELAGLRPGDSVLITAASSSVGLAAIQIANAAGATVIATTRTSEKRDALLALG 189

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755506731 187 FDVAFNYKTVKSLEEALRTASPDGYDCYFDNVGGEFSNAVILQMKTFGRIAICGAISQynRTGPCPQGTLLLQMPSPRG 265
Cdd:cd08268  190 AAHVIVTDEEDLVAEVLRITGGKGVDVVFDPVGGPQFAKLADALAPGGTLVVYGALSG--EPTPFPLKAALKKSLTFRG 266

enoyl reductase of polyketide synthase; Putative enoyl reductase of polyketide synthase. Polyketide synthases produce polyketides in step by step mechanism that is similar to fatty acid synthesis. Enoyl reductase reduces a double to single bond. Erythromycin is one example of a polyketide generated by 3 complex enzymes (megasynthases). 2-enoyl thioester reductase (ETR) catalyzes the NADPH-dependent dependent conversion of trans-2-enoyl acyl carrier protein/coenzyme A (ACP/CoA) to acyl-(ACP/CoA) in fatty acid synthesis. 2-enoyl thioester reductase activity has been linked in Candida tropicalis as essential in maintaining mitiochondrial respiratory function. This ETR family is a part of the medium chain dehydrogenase/reductase family, but lack the zinc coordination sites characteristic of the alcohol dehydrogenases in this family. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes or ketones. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which has a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site, and a structural zinc in a lobe of the catalytic domain. NAD(H) binding occurs in the cleft between the catalytic and coenzyme-binding domains, at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  36 EVLLEALFLSVDPYMRVAAKKLKEGDRMMGEQVARVVE--SKNSAFPKGTIVAALL--GWTSHSISDGNGLTKLPvewpD 111
Cdd:cd05195    4 EVEVKAAGLNFRDVLVALGLLPGDETPLGLECSGIVTRvgSGVTGLKVGDRVMGLApgAFATHVRVDARLVVKIP----D 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 112 KLPLSLAlGTVGMPGLTAYFGLLDICGVKGGETVMVSAAAGAVGSVVGQIAKLKGCKVVGTAGSDEKVAYLKKLGFDVA- 190
Cdd:cd05195   80 SLSFEEA-ATLPVAYLTAYYALVDLARLQKGESVLIHAAAGGVGQAAIQLAQHLGAEVFATVGSEEKREFLRELGGPVDh 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 755506731 191 -FNYKTVKSLEEALRTASPDGYDCYFDNVGGEFSNAVILQMKTFGRI 236
Cdd:cd05195  159 iFSSRDLSFADGILRATGGRGVDVVLNSLSGELLRASWRCLAPFGRF 205

Possible enoyl reductase; Member identified as possible enoyl reductase of the MDR family. 2-enoyl thioester reductase (ETR) catalyzes the NADPH-dependent dependent conversion of trans-2-enoyl acyl carrier protein/coenzyme A (ACP/CoA) to acyl-(ACP/CoA) in fatty acid synthesis. 2-enoyl thioester reductase activity has been linked in Candida tropicalis as essential in maintaining mitiochondrial respiratory function. This ETR family is a part of the medium chain dehydrogenase/reductase family, but lack the zinc coordination sites characteristic of the alcohol dehydrogenases in this family. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which has a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site, and a structural zinc in a lobe of the catalytic domain. NAD(H) binding occurs in the cleft between the catalytic and coenzyme-binding domains at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding. Candida tropicalis enoyl thioester reductase (Etr1p) catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters in mitochondrial fatty acid synthesis. Etr1p forms homodimers, with each subunit containing a nucleotide-binding Rossmann fold domain and a catalytic domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 106 PVEWPDKLPLSLALGT---VGMPGLTAyFGLLDICGVKGGETVMVSAAAGAVGSVVGQIAKLKGCKVVGTAGSDEKVAYL 182
Cdd:cd08244  105 DVDSLHPVPDGLDLEAavaVVHDGRTA-LGLLDLATLTPGDVVLVTAAAGGLGSLLVQLAKAAGATVVGAAGGPAKTALV 183

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755506731 183 KKLGFDVAFNYKTVKSLEEALRTASPDGYDCYFDNVGGEFSNAVILQMKTFGRIAICGAIS 243
Cdd:cd08244  184 RALGADVAVDYTRPDWPDQVREALGGGGVTVVLDGVGGAIGRAALALLAPGGRFLTYGWAS 244

2-enoyl thioester reductase (ETR); 2-enoyl thioester reductase (ETR) catalyzes the NADPH-dependent conversion of trans-2-enoyl acyl carrier protein/coenzyme A (ACP/CoA) to acyl-(ACP/CoA) in fatty acid synthesis. 2-enoyl thioester reductase activity has been linked in Candida tropicalis as essential in maintaining mitiochondrial respiratory function. This ETR family is a part of the medium chain dehydrogenase/reductase family, but lack the zinc coordination sites characteristic of the alcohol dehydrogenases in this family. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. Alcohol dehydrogenase in the liver converts ethanol and NAD+ to acetaldehyde and NADH, while in yeast and some other microorganisms ADH catalyzes the conversion acetaldehyde to ethanol in alcoholic fermentation. ADH is a member of the medium chain alcohol dehydrogenase family (MDR), which has a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The NAD(H)-binding region is comprised of 2 structurally similar halves, each of which contacts a mononucleotide. The N-terminal catalytic domain has a distant homology to GroES. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site, and a structural zinc in a lobe of the catalytic domain. NAD(H) binding occurs in the cleft between the catalytic and coenzyme-binding domains, at the active site, and coenzyme binding induces a conformational closing of this cleft. Coenzyme binding typically precedes and contributes to substrate binding. Candida tropicalis enoyl thioester reductase (Etr1p) catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters in mitochondrial fatty acid synthesis. Etr1p forms homodimers, with each subunit containing a nucleotide-binding Rossmann fold domain and a catalytic domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731   4 AKSWTLKKHfeGFPTDGnFELKTTELPP-LNNGEVLLEALFLSVDP---------YMrVAAKKLKEGDRMMG-EQVARVV 72
Cdd:cd08290    1 AKALVYTEH--GEPKEV-LQLESYEIPPpGPPNEVLVKMLAAPINPadinqiqgvYP-IKPPTTPEPPAVGGnEGVGEVV 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731  73 E--SKNSAFPKGTIV---AALLG-WTSHSISDGNGLTKLPvewPDKLPLSLALGTVGMPglTAYFGLLDICGVKGGETVM 146
Cdd:cd08290   77 KvgSGVKSLKPGDWViplRPGLGtWRTHAVVPADDLIKVP---NDVDPEQAATLSVNPC--TAYRLLEDFVKLQPGDWVI 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755506731 147 VSAAAGAVGSVVGQIAKLKGCKVVGT----AGSDEKVAYLKKLGFDVAFNYKTVKSLE--EALRTASPDGYDCYFDNVGG 220
Cdd:cd08290  152 QNGANSAVGQAVIQLAKLLGIKTINVvrdrPDLEELKERLKALGADHVLTEEELRSLLatELLKSAPGGRPKLALNCVGG 231