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 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRINTDRGTMLNDGKTRFSKDGKPIYHFLGTSTFSEYT 80
Cdd:cd08301   67 IVESVGEGVTDLKPGDHVLPVFTGECKECRHCKSEKSNMCDLLRINTDRGVMINDGKSRFSINGKPIYHFVGTSTFSEYT 146

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  81 VVHSGCVAKINPDAPLDKVCVLSCGISTGMGATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLNASRAN 160
Cdd:cd08301  147 VVHVGCVAKINPEAPLDKVCLLSCGVSTGLGAAWNVAKVKKGSTVAIFGLGAVGLAVAEGARIRGASRIIGVDLNPSKFE 226

                 .
gi 567498124 161 E 161
Cdd:cd08301  227 Q 227

Plant alcohol dehydrogenase; 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. There are 7 vertebrate ADH 7 classes, 6 of which have been identified in humans. Class III, glutathione-dependent formaldehyde dehydrogenase, has been identified as the primordial form and exists in diverse species, including plants, micro-organisms, vertebrates, and invertebrates. Class I, typified by liver dehydrogenase, is an evolving form. Gene duplication and functional specialization of ADH into ADH classes and subclasses created numerous forms in vertebrates. For example, the A, B and C (formerly alpha, beta, gamma) human class I subunits have high overall structural similarity, but differ in the substrate binding pocket and therefore in substrate specificity. In human ADH catalysis, the zinc ion helps coordinate the alcohol, followed by deprotonation of a histidine (His-51), the ribose of NAD, a serine (Ser-48) , 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. 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 an 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRINTDRGTMLNDGKTRFSKDGKPIYHFLGTSTFSEYT 80
Cdd:cd08301   67 IVESVGEGVTDLKPGDHVLPVFTGECKECRHCKSEKSNMCDLLRINTDRGVMINDGKSRFSINGKPIYHFVGTSTFSEYT 146

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  81 VVHSGCVAKINPDAPLDKVCVLSCGISTGMGATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLNASRAN 160
Cdd:cd08301  147 VVHVGCVAKINPEAPLDKVCLLSCGVSTGLGAAWNVAKVKKGSTVAIFGLGAVGLAVAEGARIRGASRIIGVDLNPSKFE 226

                 .
gi 567498124 161 E 161
Cdd:cd08301  227 Q 227

Zn-dependent alcohol/formaldehyde dehydrogenase [Energy production and conversion];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRINTDRGTMLnDGKTRFS-KDGKPIYHFLGTSTFSEY 79
Cdd:COG1062   55 VVEEVGPGVTGVAPGDHVVLSFIPSCGHCRYCASGRPALCEAGAALNGKGTLP-DGTSRLSsADGEPVGHFFGQSSFAEY 133

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 567498124  80 TVVHSGCVAKINPDAPLDKVCVLSCGISTGMGATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLNASR 158
Cdd:COG1062  134 AVVPERSVVKVDKDVPLELAALLGCGVQTGAGAVLNTAKVRPGDTVAVFGLGGVGLSAVQGARIAGASRIIAVDPVPEK 212

Plant alcohol dehydrogenase; 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. There are 7 vertebrate ADH 7 classes, 6 of which have been identified in humans. Class III, glutathione-dependent formaldehyde dehydrogenase, has been identified as the primordial form and exists in diverse species, including plants, micro-organisms, vertebrates, and invertebrates. Class I, typified by liver dehydrogenase, is an evolving form. Gene duplication and functional specialization of ADH into ADH classes and subclasses created numerous forms in vertebrates. For example, the A, B and C (formerly alpha, beta, gamma) human class I subunits have high overall structural similarity, but differ in the substrate binding pocket and therefore in substrate specificity. In human ADH catalysis, the zinc ion helps coordinate the alcohol, followed by deprotonation of a histidine (His-51), the ribose of NAD, a serine (Ser-48) , 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. 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 an 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRINTDRGTMLNDGKTRFSKDGKPIYHFLGTSTFSEYT 80
Cdd:cd08301   67 IVESVGEGVTDLKPGDHVLPVFTGECKECRHCKSEKSNMCDLLRINTDRGVMINDGKSRFSINGKPIYHFVGTSTFSEYT 146

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  81 VVHSGCVAKINPDAPLDKVCVLSCGISTGMGATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLNASRAN 160
Cdd:cd08301  147 VVHVGCVAKINPEAPLDKVCLLSCGVSTGLGAAWNVAKVKKGSTVAIFGLGAVGLAVAEGARIRGASRIIGVDLNPSKFE 226

                 .
gi 567498124 161 E 161
Cdd:cd08301  227 Q 227

class III alcohol dehydrogenases; Members identified as glutathione-dependent formaldehyde dehydrogenase(FDH), a member of the zinc dependent/medium chain alcohol dehydrogenase family. FDH converts formaldehyde and NAD(P) to formate and NAD(P)H. The initial step in this process the spontaneous formation of a S-(hydroxymethyl)glutathione adduct from formaldehyde and glutathione, followed by FDH-mediated oxidation (and detoxification) of the adduct to S-formylglutathione. MDH family uses NAD(H) as a cofactor in the interconversion of alcohols and aldehydes or ketones. Like many zinc-dependent alcohol dehydrogenases (ADH) of the medium chain alcohol dehydrogenase/reductase family (MDR), these FDHs form dimers, with 4 zinc ions per dimer. The medium chain alcohol dehydrogenase family (MDR) have 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. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRINTDRGtMLNDGKTRFSKDGKPIYHFLGTSTFSEYT 80
Cdd:cd08300   67 IVESVGEGVTSVKPGDHVIPLYTPECGECKFCKSGKTNLCQKIRATQGKG-LMPDGTSRFSCKGKPIYHFMGTSTFSEYT 145

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 567498124  81 VVHSGCVAKINPDAPLDKVCVLSCGISTGMGATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLNASR 158
Cdd:cd08300  146 VVAEISVAKINPEAPLDKVCLLGCGVTTGYGAVLNTAKVEPGSTVAVFGLGAVGLAVIQGAKAAGASRIIGIDINPDK 223

class I, II, IV alcohol dehydrogenases; NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes or ketones. This group includes alcohol dehydrogenases corresponding to mammalian classes I, II, IV. 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 (His-51), the ribose of NAD, a serine (Ser-48) , 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 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRINTDRGTMLnDGKTRFSKDGKPIYHFLGTSTFSEYT 80
Cdd:cd08299   71 IVESVGEGVTTVKPGDKVIPLFVPQCGKCRACLNPESNLCLKNDLGKPQGLMQ-DGTSRFTCKGKPIHHFLGTSTFSEYT 149

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 567498124  81 VVHSGCVAKINPDAPLDKVCVLSCGISTGMGATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLN 155
Cdd:cd08299  150 VVDEIAVAKIDAAAPLEKVCLIGCGFSTGYGAAVNTAKVTPGSTCAVFGLGGVGLSAIMGCKAAGASRIIAVDIN 224

Alcohol dehydrogenase-like

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRINTdRGTMLNDGKTRFSKDGKPIYHFLGTSTFSEYT 80
Cdd:PLN02827  74 IVESIGEGVTEFEKGDHVLTVFTGECGSCRHCISGKSNMCQVLGLER-KGVMHSDQKTRFSIKGKPVYHYCAVSSFSEYT 152

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  81 VVHSGCVAKINPDAPLDKVCVLSCGISTGMGATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLNASRAN 160
Cdd:PLN02827 153 VVHSGCAVKVDPLAPLHKICLLSCGVAAGLGAAWNVADVSKGSSVVIFGLGTVGLSVAQGAKLRGASQIIGVDINPEKAE 232

                 .
gi 567498124 161 E 161
Cdd:PLN02827 233 K 233

Class III alcohol dehydrogenase; Glutathione-dependent formaldehyde dehydrogenases (FDHs, Class III ADH) are members of the zinc-dependent/medium chain alcohol dehydrogenase family. FDH converts formaldehyde and NAD(P) to formate and NAD(P)H. The initial step in this process the spontaneous formation of a S-(hydroxymethyl)glutathione adduct from formaldehyde and glutathione, followed by FDH-mediated oxidation (and detoxification) of the adduct to S-formylglutathione. 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. Class III ADH are also known as glutathione-dependent formaldehyde dehydrogenase (FDH), which convert aldehydes to corresponding carboxylic acid and alcohol. 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 an 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLlrINTDRGTMLNDGKTRFSKDGKPIYHFLGTSTFSEYT 80
Cdd:cd08279   64 VVEEVGPGVTGVKPGDHVVLSWIPACGTCRYCSRGQPNLCDL--GAGILGGQLPDGTRRFTADGEPVGAMCGLGTFAEYT 141

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 567498124  81 VVHSGCVAKINPDAPLDKVCVLSCGISTGMGATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLNASR 158
Cdd:cd08279  142 VVPEASVVKIDDDIPLDRAALLGCGVTTGVGAVVNTARVRPGDTVAVIGCGGVGLNAIQGARIAGASRIIAVDPVPEK 219

Zinc-dependent alcohol dehydrogenases (ADH) and class III ADG (AKA formaldehyde dehydrogenase); NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes or ketones. This group contains members identified as zinc dependent alcohol dehydrogenases (ADH), and class III ADG (aka formaldehyde dehydrogenase, FDH). 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. 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. Class III ADH are also know as glutathione-dependent formaldehyde dehydrogenase (FDH), which convert aldehydes to the corresponding carboxylic acid and alcohol. 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 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRINTDRGTMLNDGKtRFSKDGKPIYHFLGTSTFSEYT 80
Cdd:cd08281   72 VVVEVGEGVTDLEVGDHVVLVFVPSCGHCRPCAEGRPALCEPGAAANGAGTLLSGGR-RLRLRGGEINHHLGVSAFAEYA 150

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 567498124  81 VVHSGCVAKINPDAPLDKVCVLSCGISTGMGATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLNASR 158
Cdd:cd08281  151 VVSRRSVVKIDKDVPLEIAALFGCAVLTGVGAVVNTAGVRPGQSVAVVGLGGVGLSALLGAVAAGASQVVAVDLNEDK 228

Threonine dehydrogenase or related Zn-dependent dehydrogenase [Amino acid transport and metabolism, General function prediction only]; Threonine dehydrogenase or related Zn-dependent dehydrogenase is part of the Pathway/BioSystem: Non-phosphorylated Entner-Doudoroff pathway

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRINtdrGTMLNDGktrfskdgkpiyhflgtsTFSEYT 80
Cdd:COG1063   64 EVVEVGEGVTGLKVGDRVVVEPNIPCGECRYCRRGRYNLCENLQFL---GIAGRDG------------------GFAEYV 122

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 567498124  81 VVHSGCVAKInPDAPLDKVCVLSCGISTGMGAtLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLNASR 158
Cdd:COG1063  123 RVPAANLVKV-PDGLSDEAAALVEPLAVALHA-VERAGVKPGDTVLVIGAGPIGLLAALAARLAGAARVIVVDRNPER 198

Glutathione-dependent formaldehyde dehydrogenase related proteins, child 1; Members identified as glutathione-dependent formaldehyde dehydrogenase(FDH), a member of the zinc-dependent/medium chain alcohol dehydrogenase family. FDH converts formaldehyde and NAD(P) to formate and NAD(P)H. The initial step in this process the spontaneous formation of a S-(hydroxymethyl)glutathione adduct from formaldehyde and glutathione, followed by FDH-mediated oxidation (and detoxification) of the adduct to S-formylglutathione. MDH family uses NAD(H) as a cofactor in the interconversion of alcohols and aldehydes, or ketones. Like many zinc-dependent alcohol dehydrogenases (ADH) of the medium chain alcohol dehydrogenase/reductase family (MDR), these FDHs form dimers, with 4 zinc ions per dimer. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDllriNTdrgtmlNDGKTRFSKDGKPIYHFLGTSTFS--- 77
Cdd:cd08283   65 VVEEVGPEVRNLKVGDRVVVPFTIACGECFYCKRGLYSQCD----NT------NPSAEMAKLYGHAGAGIFGYSHLTggy 134

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  78 -----EYTVV---HSGCVaKINPDAPLDKVCVLSCGISTG-MGATLnvAKPKKGMSVAVFGLGAVGLAAAEGARIAGASR 148
Cdd:cd08283  135 aggqaEYVRVpfaDVGPF-KIPDDLSDEKALFLSDILPTGyHAAEL--AEVKPGDTVAVWGCGPVGLFAARSAKLLGAER 211

                        170
                 ....*....|
gi 567498124 149 IIGIDLNASR 158
Cdd:cd08283  212 VIAIDRVPER 221

Formaldehyde dehydrogenases; Formaldehyde dehydrogenase (FDH) is a member of the zinc-dependent/medium chain alcohol dehydrogenase family. Formaldehyde dehydrogenase (aka ADH3) may be the ancestral form of alcohol dehydrogenase, which evolved to detoxify formaldehyde. This CD contains glutathione dependant FDH, glutathione independent FDH, and related alcohol dehydrogenases. FDH converts formaldehyde and NAD(P) to formate and NAD(P)H. The initial step in this process the spontaneous formation of a S-(hydroxymethyl)glutathione adduct from formaldehyde and glutathione, followed by FDH-mediated oxidation (and detoxification) of the adduct to S-formylglutathione. Unlike typical FDH, Pseudomonas putida aldehyde-dismutating FDH (PFDH) is glutathione-independent. The medium chain alcohol dehydrogenase family (MDR) have 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   2 VESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCdllrintdrGTMLNDGKTRFSKDGkpiyhflgtsTFSEYTV 81
Cdd:cd05278   66 VVEVGSDVKRLKPGDRVSVPCITFCGRCRFCRRGYHAHC---------ENGLWGWKLGNRIDG----------GQAEYVR 126

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  82 VH--SGCVAKINPDAPLDKVCVLSCGISTGM-GATLNVAKPkkGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLNASR 158
Cdd:cd05278  127 VPyaDMNLAKIPDGLPDEDALMLSDILPTGFhGAELAGIKP--GSTVAVIGAGPVGLCAVAGARLLGAARIIAVDSNPER 204

6-hydroxycyclohex-1-ene-1-carboxyl-CoA dehydrogenase, N-benzyl-3-pyrrolidinol dehydrogenase, and other MDR family members; This group contains enzymes of the zinc-dependent alcohol dehydrogenase family, including members (aka MDR) identified as 6-hydroxycyclohex-1-ene-1-carboxyl-CoA dehydrogenase and N-benzyl-3-pyrrolidinol dehydrogenase. 6-hydroxycyclohex-1-ene-1-carboxyl-CoA dehydrogenase catalyzes the conversion of 6-Hydroxycyclohex-1-enecarbonyl-CoA and NAD+ to 6-Ketoxycyclohex-1-ene-1-carboxyl-CoA,NADH, and H+. This group displays the characteristic catalytic and structural zinc sites of the zinc-dependent alcohol dehydrogenases. 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 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCdllrintdrgtmLNDGKTRFSKDGkpiyhflgtsTFSEYT 80
Cdd:cd08254   67 TVVEVGAGVTNFKVGDRVAVPAVIPCGACALCRRGRGNLC------------LNQGMPGLGIDG----------GFAEYI 124

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 567498124  81 VVHSGCVAKINPDAPLDKVCVLSCGISTGMGATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGAsRIIGIDLNASR 158
Cdd:cd08254  125 VVPARALVPVPDGVPFAQAAVATDAVLTPYHAVVRAGEVKPGETVLVIGLGGLGLNAVQIAKAMGA-AVIAVDIKEEK 201

Glutathione-dependent formaldehyde dehydrogenase related proteins, child 2; Glutathione-dependent formaldehyde dehydrogenases (FDHs) are members of the zinc-dependent/medium chain alcohol dehydrogenase family. Formaldehyde dehydrogenase (FDH) is a member of the zinc-dependent/medium chain alcohol dehydrogenase family. FDH converts formaldehyde and NAD to formate and NADH. The initial step in this process the spontaneous formation of a S-(hydroxymethyl)glutathione adduct from formaldehyde and glutathione, followed by FDH-mediated oxidation (and detoxification) of the adduct to S-formylglutathione. These tetrameric FDHs have a catalytic zinc that resides between the catalytic and NAD(H)binding domains and a structural zinc in a lobe of the catalytic domain. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   2 VESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDllrintdRGTMlndgktrFSKDGKPIyhfLGTSTfSEYTV 81
Cdd:cd08284   65 VVEVGPEVRTLKVGDRVVSPFTIACGECFYCRRGQSGRCA-------KGGL-------FGYAGSPN---LDGAQ-AEYVR 126

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 567498124  82 V--HSGCVAKINPDAPLDKVCVLSCGISTGMGATLNvAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDLNASR 158
Cdd:cd08284  127 VpfADGTLLKLPDGLSDEAALLLGDILPTGYFGAKR-AQVRPGDTVAVIGCGPVGLCAVLSAQVLGAARVFAVDPVPER 204

L-threonine dehydrogenase; L-threonine dehydrogenase (TDH) catalyzes the zinc-dependent formation of 2-amino-3-ketobutyrate from L-threonine, via NAD(H)-dependent oxidation. THD is a member of the zinc-requiring, medium chain NAD(H)-dependent alcohol dehydrogenase family (MDR). MDRs have a NAD(P)(H)-binding domain in a Rossmann fold of a beta-alpha form. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. 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. Sorbitol and aldose reductase are NAD(+) binding proteins of the polyol pathway, which interconverts glucose and fructose.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   1 IVESVGEGVTELKPGDKVL--P-IFtgeCGQCRHCKSEESNMCD---LLRINTDRGtmlndgktrfskdgkpiyhflgts 74
Cdd:cd08234   63 VVVAVGSKVTGFKVGDRVAvdPnIY---CGECFYCRRGRPNLCEnltAVGVTRNGG------------------------ 115

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  75 tFSEYTVVHSGCVAKINPDAPLDKVCV---LSCGIStGMgatlNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIG 151
Cdd:cd08234  116 -FAEYVVVPAKQVYKIPDNLSFEEAALaepLSCAVH-GL----DLLGIKPGDSVLVFGAGPIGLLLAQLLKLNGASRVTV 189

                 ....*..
gi 567498124 152 IDLNASR 158
Cdd:cd08234  190 AEPNEEK 196

Alcohol dehydrogenases of the MDR family; NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. This group contains proteins that share the characteristic catalytic and structural zinc-binding sites of the zinc-dependent alcohol dehydrogenase family. 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 (His-51), the ribose of NAD, a serine (Ser-48), 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 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRintdrgtmlndgktrfskdgkpIYHFLGTSTFSEYT 80
Cdd:cd08259   65 TVEEVGEGVERFKPGDRVILYYYIPCGKCEYCLSGEENLCRNRA----------------------EYGEEVDGGFAEYV 122

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  81 VVHSGCVAKINPDAPLDKVCVLSCGISTGMGAtLNVAKPKKGMSVAV-FGLGAVGLAAAEGARIAGAsRIIGIDLNASRA 159
Cdd:cd08259  123 KVPERSLVKLPDNVSDESAALAACVVGTAVHA-LKRAGVKKGDTVLVtGAGGGVGIHAIQLAKALGA-RVIAVTRSPEKL 200

Pseudomonas putida aldehyde-dismutating formaldehyde dehydrogenase (PFDH); Formaldehyde dehydrogenase (FDH) is a member of the zinc-dependent/medium chain alcohol dehydrogenase family. Unlike typical FDH, Pseudomonas putida aldehyde-dismutating FDH (PFDH) is glutathione-independent. PFDH converts 2 molecules of aldehydes to corresponding carboxylic acid and alcohol. MDH family uses NAD(H) as a cofactor in the interconversion of alcohols and aldehydes, or ketones. Like the zinc-dependent alcohol dehydrogenases (ADH) of the medium chain alcohol dehydrogenase/reductase family (MDR), these tetrameric FDHs have a catalytic zinc that resides between the catalytic and NAD(H)binding domains and a structural zinc in a lobe of the catalytic domain. Unlike ADH, where NAD(P)(H) acts as a cofactor, NADH in FDH is a tightly bound redox cofactor (similar to nicotinamide proteins). The medium chain alcohol dehydrogenase family (MDR) has a NAD(P)(H)-binding domain in a Rossmann fold of an 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCdlLRINTDRgtmlnDGKTRFSKDGKPiyhFLGTStfSEYT 80
Cdd:cd08282   64 EVEEVGSAVESLKVGDRVVVPFNVACGRCRNCKRGLTGVC--LTVNPGR-----AGGAYGYVDMGP---YGGGQ--AEYL 131

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  81 VV---HSGCVaKINPDAP----LDKVCvLSCGISTG-MGATLNVAKPkkGMSVAVFGLGAVGLAAAEGARIAGASRIIGI 152
Cdd:cd08282  132 RVpyaDFNLL-KLPDRDGakekDDYLM-LSDIFPTGwHGLELAGVQP--GDTVAVFGAGPVGLMAAYSAILRGASRVYVV 207

                 ....*.
gi 567498124 153 DLNASR 158
Cdd:cd08282  208 DHVPER 213

Sorbitol dehydrogenase; 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. Aldose reductase catalyzes the NADP(H)-dependent conversion of glucose to sorbital, and SDH uses NAD(H) in the conversion of sorbitol to fructose. NAD(P)(H)-dependent oxidoreductases are the major enzymes in the interconversion of alcohols and aldehydes, or ketones. The medium chain alcohol dehydrogenase family (MDR) have 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124   1 IVESVGEGVTELKPGDKV-----LPiftgeCGQCRHCKSEESNMCDLLRIntdRGTMLNDGktrfskdgkpiyhflgtsT 75
Cdd:cd05285   65 TVVAVGSGVTHLKVGDRVaiepgVP-----CRTCEFCKSGRYNLCPDMRF---AATPPVDG------------------T 118

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  76 FSEYTVVHSGCVAKInPDA----------PLdKVCVLSCgistgmgatlNVAKPKKGMSVAVFGLGAVGLAAAEGARIAG 145
Cdd:cd05285  119 LCRYVNHPADFCHKL-PDNvsleegalvePL-SVGVHAC----------RRAGVRPGDTVLVFGAGPIGLLTAAVAKAFG 186

                        170
                 ....*....|...
gi 567498124 146 ASRIIGIDLNASR 158
Cdd:cd05285  187 ATKVVVTDIDPSR 199

Alcohol dehydrogenases of the MDR family; This group contains members identified as related to zinc-dependent alcohol dehydrogenase and other members of the MDR 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. The MDR group includes various 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 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRIntdRGTMlndgktrfsKDGkpiyhflgtsTFSEYT 80
Cdd:cd08261   64 EVVEVGEGVAGLKVGDRVVVDPYISCGECYACRKGRPNCCENLQV---LGVH---------RDG----------GFAEYI 121

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 567498124  81 VVHSGCVaKINPDAPLDKVCVLSCgISTGMGATlNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGAsRIIGIDLNASR 158
Cdd:cd08261  122 VVPADAL-LVPEGLSLDQAALVEP-LAIGAHAV-RRAGVTAGDTVLVVGAGPIGLGVIQVAKARGA-RVIVVDIDDER 195

L-iditol 2-dehydrogenase; Putative L-iditol 2-dehydrogenase based on annotation of some members in this subgroup. L-iditol 2-dehydrogenase catalyzes the NAD+-dependent conversion of L-iditol to L-sorbose in fructose and mannose metabolism. This enzyme is related to sorbitol dehydrogenase, alcohol dehydrogenase, and other medium chain dehydrogenase/reductases. The zinc-dependent alcohol dehydrogenase (ADH-Zn)-like family of proteins is a diverse group of proteins related to the first identified member, class I mammalian ADH. This group is also called the medium chain dehydrogenases/reductase family (MDR) to highlight its broad range of activities and to distinguish 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 GroES-like catalytic domain. 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 567498124   1 IVESVGEGVTELKPGDKVLPIFTGECGQCRHCKSEESNMCDLLRINTdrgtmlndgktrFSKDGkpiyhflgtsTFSEYT 80
Cdd:cd08235   64 EIVEVGDGVTGFKVGDRVFVAPHVPCGECHYCLRGNENMCPNYKKFG------------NLYDG----------GFAEYV 121

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  81 VVHS-----GCVAKInPD------APLdkVCVLSCGIstgmgATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRI 149
Cdd:cd08235  122 RVPAwavkrGGVLKL-PDnvsfeeAAL--VEPLACCI-----NAQRKAGIKPGDTVLVIGAGPIGLLHAMLAKASGARKV 193

                 ....*....
gi 567498124 150 IGIDLNASR 158
Cdd:cd08235  194 IVSDLNEFR 202

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 567498124   1 IVESVGEGVTELKPGDKVL--PIFTgeCGQCRHCKSEESNMCDLLR---INTDRGtmlndgktrfskdgkpiyhflgtst 75
Cdd:cd05284   68 WVEEVGSGVDGLKEGDPVVvhPPWG--CGTCRYCRRGEENYCENARfpgIGTDGG------------------------- 120

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 567498124  76 FSEYTVVHSGCVAKINPDAPLDKVCVLSC-GISTGMGATLNVAKPKKGMSVAVFGLGAVGLAAAEGARIAGASRIIGIDL 154
Cdd:cd05284  121 FAEYLLVPSRRLVKLPRGLDPVEAAPLADaGLTAYHAVKKALPYLDPGSTVVVIGVGGLGHIAVQILRALTPATVIAVDR 200

                 ....
gi 567498124 155 NASR 158
Cdd:cd05284  201 SEEA 204