NADPH-dependent curcumin reductase CurA [Secondary metabolites biosynthesis, transport and catabolism, General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622   1 MPGLTSLIGIQEKGHITAGsnKTMVVSGAAGACGSVAGQIGHFLGCsRVVGICGTHEKCILLTSELGFDAAINYKKDNVA 80
Cdd:COG2130   129 MPGLTAYFGLLDIGKPKAG--ETVVVSAAAGAVGSVVGQIAKLKGC-RVVGIAGGAEKCRYLVEELGFDAAIDYKAGDLA 205

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  81 EQLRESCPAGVDVYFDNVGGNISDTVISQMNENSHIILCGQISQYNKDvpyPPPLSPAIEAIQKERNITRERFLVLNYKD 160
Cdd:COG2130   206 AALAAACPDGIDVYFDNVGGEILDAVLPLLNTFARIAVCGAISQYNAT---EPPPGPRNLGQLLVKRLRMQGFIVFDHAD 282

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1700447622 161 KFEPGILQLSQWFKEGKLKIKETVINGLENMGAAFQSMMTGGNIGKQIV 209
Cdd:COG2130   283 RFPEFLAELAGWVAEGKLKYRETVVEGLENAPEAFLGLFEGENFGKLLV 331

putative allyl alcohol dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622   1 MPGLTSLIGIQEKGHITAGSNktMVVSGAAGACGSVAGQIGHFLGCSrVVGICGTHEKCILLTSELGFDAAINYKKD-NV 79
Cdd:PLN03154  141 MAGFTAYAGFYEVCSPKKGDS--VFVSAASGAVGQLVGQLAKLHGCY-VVGSAGSSQKVDLLKNKLGFDEAFNYKEEpDL 217

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  80 AEQLRESCPAGVDVYFDNVGGNISDTVISQMNENSHIILCGQISQynKDVPYPPPLSPAIEAIQKErnITRERFLVLNYK 159
Cdd:PLN03154  218 DAALKRYFPEGIDIYFDNVGGDMLDAALLNMKIHGRIAVCGMVSL--NSLSASQGIHNLYNLISKR--IRMQGFLQSDYL 293

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1700447622 160 DKFEPGILQLSQWFKEGKLKIKETVINGLENMGAAFQSMMTGGNIGKQIVCISEE 214
Cdd:PLN03154  294 HLFPQFLENVSRYYKQGKIVYIEDMSEGLESAPAALVGLFSGKNVGKQVIRVAKE 348

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 1700447622   1 MPGLTSLIGIQEKGHITAGsnKTMVVSGAAGACGSVAGQIGHFLGCsRVVGICGTHEKCILLTSELGFDAAINYKKDNVA 80
Cdd:cd05288   128 MTGLTAYFGLTEIGKPKPG--ETVVVSAAAGAVGSVVGQIAKLLGA-RVVGIAGSDEKCRWLVEELGFDAAINYKTPDLA 204

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  81 EQLRESCPAGVDVYFDNVGGNISDTVISQMNENSHIILCGQISQYNKDVPYPPPLSPAIeaiqKERNITRERFLVLNYKD 160
Cdd:cd05288   205 EALKEAAPDGIDVYFDNVGGEILDAALTLLNKGGRIALCGAISQYNATEPPGPKNLGNI----ITKRLTMQGFIVSDYAD 280

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1700447622 161 KFEPGILQLSQWFKEGKLKIKETVINGLENMGAAFQSMMTGGNIGKQIV 209
Cdd:cd05288   281 RFPEALAELAKWLAEGKLKYREDVVEGLENAPEAFLGLFTGKNTGKLVV 329

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 1700447622   1 MPGLTSLIGIQEKGHITAGsnKTMVVSGAAGACGSVAGQIGHFLGCsRVVGICGTHEKCILLtSELGFDAAINYKKDNVA 80
Cdd:cd08294   126 MPGLTAYFGLLEICKPKAG--ETVVVNGAAGAVGSLVGQIAKIKGC-KVIGCAGSDDKVAWL-KELGFDAVFNYKTVSLE 201

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  81 EQLRESCPAGVDVYFDNVGGNISDTVISQMNENSHIILCGQISQYN-KDVPYPPPLSPAIeaIQKErnITRERFLVLNYK 159
Cdd:cd08294   202 EALKEAAPDGIDCYFDNVGGEFSSTVLSHMNDFGRVAVCGSISTYNdKEPKKGPYVQETI--IFKQ--LKMEGFIVYRWQ 277

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1700447622 160 DKFEPGILQLSQWFKEGKLKIKETVINGLENMGAAFQSMMTGGNIGKQIV 209
Cdd:cd08294   278 DRWPEALKQLLKWIKEGKLKYREHVTEGFENMPQAFIGMLKGENTGKAIV 327

leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase; Leukotriene B4 12-hydroxydehydrogenase is an NADP-dependent enzyme of arachidonic acid metabolism, responsible for converting leukotriene B4 to the much less active metabolite 12-oxo-leukotriene B4. The BRENDA database lists leukotriene B4 12-hydroxydehydrogenase as one of the synonyms of 2-alkenal reductase (EC 1.3.1.74), while 1.3.1.48 is 15-oxoprostaglandin 13-reductase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622   1 MPGLTSLIGIQEKGHITAGsnKTMVVSGAAGACGSVAGQIGHFLGCsRVVGICGTHEKCILLtSELGFDAAINYKK-DNV 79
Cdd:TIGR02825 121 MPGLTAYFGLLEICGVKGG--ETVMVNAAAGAVGSVVGQIAKLKGC-KVVGAAGSDEKVAYL-KKLGFDVAFNYKTvKSL 196

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  80 AEQLRESCPAGVDVYFDNVGGNISDTVISQMNENSHIILCGQISQYNKDVPYPPPLSPAIEAIQKERnitRERFLVLNYK 159
Cdd:TIGR02825 197 EETLKKASPDGYDCYFDNVGGEFSNTVIGQMKKFGRIAICGAISTYNRTGPLPPGPPPEIVIYQELR---MEGFIVNRWQ 273

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1700447622 160 -DKFEPGILQLSQWFKEGKLKIKETVINGLENMGAAFQSMMTGGNIGKQIV 209
Cdd:TIGR02825 274 gEVRQKALKELLKWVLEGKIQYKEYVIEGFENMPAAFMGMLKGENLGKTIV 324

putative allyl alcohol dehydrogenase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622   1 MPGLTSLIGIQEKGHITAGSNktMVVSGAAGACGSVAGQIGHFLGCSrVVGICGTHEKCILLTSELGFDAAINYKKD-NV 79
Cdd:PLN03154  141 MAGFTAYAGFYEVCSPKKGDS--VFVSAASGAVGQLVGQLAKLHGCY-VVGSAGSSQKVDLLKNKLGFDEAFNYKEEpDL 217

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  80 AEQLRESCPAGVDVYFDNVGGNISDTVISQMNENSHIILCGQISQynKDVPYPPPLSPAIEAIQKErnITRERFLVLNYK 159
Cdd:PLN03154  218 DAALKRYFPEGIDIYFDNVGGDMLDAALLNMKIHGRIAVCGMVSL--NSLSASQGIHNLYNLISKR--IRMQGFLQSDYL 293

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1700447622 160 DKFEPGILQLSQWFKEGKLKIKETVINGLENMGAAFQSMMTGGNIGKQIVCISEE 214
Cdd:PLN03154  294 HLFPQFLENVSRYYKQGKIVYIEDMSEGLESAPAALVGLFSGKNVGKQVIRVAKE 348

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 1700447622   4 LTSLIGIQEKGHITAGsnKTMVVSGAAGACGSVAGQIGHFLGCsRVVGICGTHEKCILLtSELGFDAAINYKKDNVAEQL 83
Cdd:cd08241   125 GTAYHALVRRARLQPG--ETVLVLGAAGGVGLAAVQLAKALGA-RVIAAASSEEKLALA-RALGADHVIDYRDPDLRERV 200

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  84 RESC-PAGVDVYFDNVGGNISDTVISQMNENSHIILCGQISqynKDVPYPPPLSPAIeaiqkeRNIT----RERFLVLNY 158
Cdd:cd08241   201 KALTgGRGVDVVYDPVGGDVFEASLRSLAWGGRLLVIGFAS---GEIPQIPANLLLL------KNISvvgvYWGAYARRE 271

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1700447622 159 KDKFEPGILQLSQWFKEGKLKIKETVINGLENMGAAFQSMMTGGNIGKQIVC 210
Cdd:cd08241   272 PELLRANLAELFDLLAEGKIRPHVSAVFPLEQAAEALRALADRKATGKVVLT 323

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 1700447622   1 MPGLTSLIGIQEKGHITAGsnKTMVVSGAAGACGSVAGQIGHFLGCsRVVGICGT--HEkciLLTSeLGFDAAINYKKDN 78
Cdd:cd05289   127 LAGLTAWQALFELGGLKAG--QTVLIHGAAGGVGSFAVQLAKARGA-RVIATASAanAD---FLRS-LGADEVIDYTKGD 199

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  79 VAEQLRescPAGVDVYFDNVGGNISDTVISQMNENSHIIlcgqisqynkDVPYPPPlspaIEAIQKERNITRERFLVLNY 158
Cdd:cd05289   200 FERAAA---PGGVDAVLDTVGGETLARSLALVKPGGRLV----------SIAGPPP----AEQAAKRRGVRAGFVFVEPD 262

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1700447622 159 KDKFEpgilQLSQWFKEGKLKIKETVINGLENMGAAFQSMMTGGNIGKQIV 209
Cdd:cd05289   263 GEQLA----ELAELVEAGKLRPVVDRVFPLEDAAEAHERLESGHARGKVVL 309

Zeta-crystallin with NADP-dependent quinone reductase activity (QOR); Zeta-crystallin is a eye lens protein with NADP-dependent quinone reductase activity (QOR). It has been cited as a structural component in mammalian eyes, but also has homology to quinone reductases in unrelated species. QOR catalyzes the conversion of a quinone and NAD(P)H to a hydroquinone and 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. 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. 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 1700447622   1 MPGLTSLIGIQEKGHITAGsnKTMVVSGAAGACGSVAGQIGHFLGCsRVVGICGTHEKcILLTSELGFDAAINYKKDNVA 80
Cdd:cd08253   127 IPALTAYRALFHRAGAKAG--ETVLVHGGSGAVGHAAVQLARWAGA-RVIATASSAEG-AELVRQAGADAVFNYRAEDLA 202

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  81 EQLRESC-PAGVDVYFDNVGGNISDTVISQMNENSHIILCGqisqyNKDVPYPPPLSPaieAIQKERNItreRFLVLnY- 158
Cdd:cd08253   203 DRILAATaGQGVDVIIEVLANVNLAKDLDVLAPGGRIVVYG-----SGGLRGTIPINP---LMAKEASI---RGVLL-Yt 270

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1700447622 159 --KDKFEPGILQLSQWFKEGKLKIKETVINGLENMGAAFQSMMTGGNIGKQIV 209
Cdd:cd08253   271 atPEERAAAAEAIAAGLADGALRPVIAREYPLEEAAAAHEAVESGGAIGKVVL 323

Medium chain reductase/dehydrogenase (MDR)/zinc-dependent alcohol dehydrogenase-like family; The medium chain reductase/dehydrogenases (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. ADH-like proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and generally 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. 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. Other MDR members have only a catalytic zinc, and some contain no coordinated zinc.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622   2 PGLTSLIGIQEKGHITAGSnkTMVVSGAaGACGSVAGQIGHFLGCsRVVGICGTHEKcILLTSELGFDAAINYKKDNVAE 81
Cdd:cd05188   118 PLATAYHALRRAGVLKPGD--TVLVLGA-GGVGLLAAQLAKAAGA-RVIVTDRSDEK-LELAKELGADHVIDYKEEDLEE 192

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1700447622  82 QLRESCPAGVDVYFDNVGGNIS-DTVISQMNENSHIILCGQISQynkdvpyPPPLSPAIEAIQKERNIT 149
Cdd:cd05188   193 ELRLTGGGGADVVIDAVGGPETlAQALRLLRPGGRIVVVGGTSG-------GPPLDDLRRLLFKELTII 254

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 1700447622   1 MPGLTSLIGIQEKGHITAGSnkTMVVSGAAGACGSVAGQIGHFLGCsRVVGICGTHEKCILLTsELGFDAAINYKKDNVA 80
Cdd:cd05286   119 LQGLTAHYLLRETYPVKPGD--TVLVHAAAGGVGLLLTQWAKALGA-TVIGTVSSEEKAELAR-AAGADHVINYRDEDFV 194

                          90       100
                  ....*....|....*....|.
gi 1700447622  81 EQLRE-SCPAGVDVYFDNVGG 100
Cdd:cd05286   195 ERVREiTGGRGVDVVYDGVGK 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 1700447622   3 GLTSLIGIQEKGHITAGsnKTMVVSGAAGACGSVAGQIGHFLgcsRVVGICGT-----HEKcillTSELGFDAAINYKKD 77
Cdd:cd08275   123 YLTAYYALFELGNLRPG--QSVLVHSAAGGVGLAAGQLCKTV---PNVTVVGTasaskHEA----LKENGVTHVIDYRTQ 193

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  78 NVAEQLRESCPAGVDVYFDNVGGniSDTVISQmnenSHIILCGQISQYN----------------KDVPYPPPLSPaIEA 141
Cdd:cd08275   194 DYVEEVKKISPEGVDIVLDALGG--EDTRKSY----DLLKPMGRLVVYGaanlvtgekrswfklaKKWWNRPKVDP-MKL 266

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1700447622 142 IqkERNITRERF---LVLNYKDKFEPGILQLSQWFKEGKLKIKETVINGLENMGAAFQSMMTGGNIGKQIV 209
Cdd:cd08275   267 I--SENKSVLGFnlgWLFEERELLTEVMDKLLKLYEEGKIKPKIDSVFPFEEVGEAMRRLQSRKNIGKVVL 335

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 1700447622   1 MPGLTSLiGIQEKGHITAGSnkTMVVSGAAGACGSVAGQIGHFLGcSRVVGICGTHEKCILLTsELGFDAAINYKKDNVA 80
Cdd:cd08244   126 HDGRTAL-GLLDLATLTPGD--VVLVTAAAGGLGSLLVQLAKAAG-ATVVGAAGGPAKTALVR-ALGADVAVDYTRPDWP 200

                          90       100
                  ....*....|....*....|...
gi 1700447622  81 EQLRESCPA-GVDVYFDNVGGNI 102
Cdd:cd08244   201 DQVREALGGgGVTVVLDGVGGAI 223

Human Reticulon 4 Interacting Protein 1; Human Reticulon 4 Interacting Protein 1 is a member of the medium chain dehydrogenase/ reductase (MDR) family. Riticulons are endoplasmic reticulum associated proteins involved in membrane trafficking and neuroendocrine secretion. The 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 1700447622   3 GLTSLIGIQEKGHI--TAGSNKTMVVSGAAGACGSVAGQIGHFLGCsRVVGICgtHEKCILLTSELGFDAAINYKKDNVA 80
Cdd:cd08248   143 GLTAWSALVNVGGLnpKNAAGKRVLILGGSGGVGTFAIQLLKAWGA-HVTTTC--STDAIPLVKSLGADDVIDYNNEDFE 219

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  81 EQLRESCPagVDVYFDNVGGNISDTVISQMNENSHIILCGQISQYNKDvPYPPPLSPAIEAIQKERNITRERFLVLNYKD 160
Cdd:cd08248   220 EELTERGK--FDVILDTVGGDTEKWALKLLKKGGTYVTLVSPLLKNTD-KLGLVGGMLKSAVDLLKKNVKSLLKGSHYRW 296

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1700447622 161 KF----EPGILQLSQWFKEGKLKikeTVIN---GLENMGAAFQSMMTGGNIGKQIV 209
Cdd:cd08248   297 GFfspsGSALDELAKLVEDGKIK---PVIDkvfPFEEVPEAYEKVESGHARGKTVI 349

NAD(P)-dependent sugar dehydrogenases; This group contains proteins identified as sorbitol dehydrogenases and other sugar dehydrogenases of the medium-chain dehydrogenase/reductase family (MDR), which includes zinc-dependent alcohol dehydrogenase and related proteins. Sorbitol and aldose reductase are NAD(+) binding proteins of the polyol pathway, which interconverts glucose and fructose. Sorbitol dehydrogenase is tetrameric and has a single catalytic zinc per subunit. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. Related proteins include threonine dehydrogenase, formaldehyde dehydrogenase, and butanediol dehydrogenase. The medium chain alcohol dehydrogenase family (MDR) has a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. The N-terminal region typically has an all-beta catalytic domain. These proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and have 2 tightly bound zinc atoms per subunit. Horse liver alcohol dehydrogenase is a dimeric enzyme and each subunit has two domains. The NAD binding domain is in a Rossmann fold and the catalytic domain contains a zinc ion to which substrates bind. There is a cleft between the domains that closes upon formation of the ternary complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  12 EKGHITAGsnKTMVVSGAaGACGSVAGQIGHFLGCSRVVGICGTHEKCILLTsELGFDAAINYKKDNVaEQLRESCPA-G 90
Cdd:cd08236   153 RLAGITLG--DTVVVIGA-GTIGLLAIQWLKILGAKRVIAVDIDDEKLAVAR-ELGADDTINPKEEDV-EKVRELTEGrG 227

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622  91 VDVYFDNVGGNIS-DTVISQMNENSHIILCGqisqynkdVPYPPPLSPAIEAiqkeRNITRERFLVL---NYKDKFEPGi 166
Cdd:cd08236   228 ADLVIEAAGSPATiEQALALARPGGKVVLVG--------IPYGDVTLSEEAF----EKILRKELTIQgswNSYSAPFPG- 294

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1700447622 167 lqlSQW------FKEGKLKIKE--TVINGLENMGAAFQsMMTGGNI 204
Cdd:cd08236   295 ---DEWrtaldlLASGKIKVEPliTHRLPLEDGPAAFE-RLADREE 336

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 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. 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 1700447622  21 NKTMVVSGAAGACGSVAGQIGHFLGCSrVVGICGTHEKCILLTSeLGFDAAINYKKDNVAEQL-RESCPAGVDVYFDNVG 99
Cdd:cd08251   121 GEHILIQTATGGTGLMAVQLARLKGAE-IYATASSDDKLEYLKQ-LGVPHVINYVEEDFEEEImRLTGGRGVDVVINTLS 198

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1700447622 100 GnisdTVIsQMNENShiilcgqisqynkdvpypppLSP-------AIEAIQKERNITRERF-------------LVLNYK 159
Cdd:cd08251   199 G----EAI-QKGLNC--------------------LAPggryveiAMTALKSAPSVDLSVLsnnqsfhsvdlrkLLLLDP 253

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1700447622 160 DKFEPGILQLSQWFKEGKLKIKETVINGLENMGAAFQSMMTGGNIGKQIV 209
Cdd:cd08251   254 EFIADYQAEMVSLVEEGELRPTVSRIFPFDDIGEAYRYLSDRENIGKVVV 303

Benzyl alcohol dehydrogenase; Benzyl alcohol dehydrogenase is similar to liver alcohol dehydrogenase, but has some amino acid substitutions near the active site, which may determine the enzyme's specificity of oxidizing aromatic substrates. Also known as aryl-alcohol dehydrogenases, they catalyze the conversion of an aromatic alcohol + NAD+ to an aromatic aldehyde + NADH + H+. 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 1700447622  17 TAGSnkTMVVSGAaGACGSVAGQIGHFLGCSRVVGIcGTHEKCILLTSELGFDAAINYKKDNVAEQLRESCPAGVDVYFD 96
Cdd:cd08278   185 RPGS--SIAVFGA-GAVGLAAVMAAKIAGCTTIIAV-DIVDSRLELAKELGATHVINPKEEDLVAAIREITGGGVDYALD 260

                  ...
gi 1700447622  97 NVG 99
Cdd:cd08278   261 TTG 263

D-arabinose dehydrogenase; This group contains arabinose dehydrogenase (AraDH) and related alcohol dehydrogenases. AraDH is a member of the medium chain dehydrogenase/reductase family and catalyzes the NAD(P)-dependent oxidation of D-arabinose and other pentoses, the initial step in the metabolism of d-arabinose into 2-oxoglutarate. Like the alcohol dehydrogenases, AraDH binds a zinc in the catalytic cleft as well as a distal structural zinc. AraDH forms homotetramers as a dimer of dimers. AraDH replaces a conserved catalytic His with replace with Arg, compared to the canonical ADH site. 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 1700447622   3 GLTSLIGIQEK-GHITAGSnkTMVVSGAAGaCGSVAGQIGHFLGCSRVVGICGTHEKcILLTSELGFDAAINyKKDNVAE 81
Cdd:cd05284   151 GLTAYHAVKKAlPYLDPGS--TVVVIGVGG-LGHIAVQILRALTPATVIAVDRSEEA-LKLAERLGADHVLN-ASDDVVE 225

                          90       100
                  ....*....|....*....|.
gi 1700447622  82 QLRES-CPAGVDVYFDNVGGN 101
Cdd:cd05284   226 EVRELtGGRGADAVIDFVGSD 246