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
                 ....*....|....*....|....*....|....*
gi 502304173   4 RAAVALQAGKPLEVMAVQLEGPRAGEVPVEVKATG 38
Cdd:cd08300    4 KAAVAWEAGKPLSIEEVEVAPPKAGEVRIKILATG 38

GNAT family N-acetyltransferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502304173  52 ELTTRELYDLLRMRVDVFVVEQNCPYPELDGKDI--DALHLRLLEGAELLGAARILKPYEPQDPSKIGRVVVSPDHRGKR 129
Cdd:PRK10314  11 ELSVSQLYALLQLRCAVFVVEQNCPYQDIDGDDLtgDNRHILGWKNDELVAYARILKSDDDLEPVVIGRVIVSEALRGEK 90

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 502304173 130 LGDALMSEAIAACERLYPENPIALSAQAHLRRFYESFGFIAVSQEYLEDGIPHIDMVRQ 188
Cdd:PRK10314  91 VGQQLMSKTLESCTRHWPDKPVYLGAQAHLQNFYQSFGFIPVTEVYEEDGIPHIGMARE 149

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
                 ....*....|....*....|....*....|....*
gi 502304173   4 RAAVALQAGKPLEVMAVQLEGPRAGEVPVEVKATG 38
Cdd:cd08300    4 KAAVAWEAGKPLSIEEVEVAPPKAGEVRIKILATG 38

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

                         10        20
                 ....*....|....*....|....*..
gi 502304173  12 GKPLEVMAVQLEGPRAGEVPVEVKATG 38
Cdd:COG1062    1 GGPLEIEEVELDEPRPGEVLVRIVAAG 27

GNAT family N-acetyltransferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502304173  52 ELTTRELYDLLRMRVDVFVVEQNCPYPELDGKDI--DALHLRLLEGAELLGAARILKPYEPQDPSKIGRVVVSPDHRGKR 129
Cdd:PRK10314  11 ELSVSQLYALLQLRCAVFVVEQNCPYQDIDGDDLtgDNRHILGWKNDELVAYARILKSDDDLEPVVIGRVIVSEALRGEK 90

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 502304173 130 LGDALMSEAIAACERLYPENPIALSAQAHLRRFYESFGFIAVSQEYLEDGIPHIDMVRQ 188
Cdd:PRK10314  91 VGQQLMSKTLESCTRHWPDKPVYLGAQAHLQNFYQSFGFIPVTEVYEEDGIPHIGMARE 149

Predicted N-acetyltransferase YhbS [General function prediction only];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 502304173 116 IGRVVVSPDHRGKRLGDALMSEAIAACERL-YPEnpIALSAQAHLRRFYESFGFIAVSQEYLEDGIPHIDMVR 187
Cdd:COG3153   70 LGPLAVDPEYRGQGIGRALMRAALEAARERgARA--VVLLGDPSLLPFYERFGFRPAGELGLTLGPDEVFLAK 140

Acetyltransferase (GNAT) family; This family contains proteins with N-acetyltransferase functions such as Elp3-related proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502304173   57 ELYDLLRmrVDVFVVEQNCPYPELDGKDIDALHLRLL--EGAELLGAARILKPYEPQDPSKIGRVVVSPDHRGKRLGDAL 134
Cdd:pfam00583   3 ALYELLS--EEFPEPWPDEPLDLLEDWDEDASEGFFVaeEDGELVGFASLSIIDDEPPVGEIEGLAVAPEYRGKGIGTAL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 502304173  135 MSEAIAA-----CERLY----PENPIAlsaqahlRRFYESFGF 168
Cdd:pfam00583  81 LQALLEWarergCERIFlevaADNLAA-------IALYEKLGF 116

Ribosomal protein S18 acetylase RimI and related acetyltransferases [Translation, ribosomal structure and biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502304173 104 ILKPYEPQDPSKIGRVVVSPDHRGKRLGDALMSEAIAA-----CERLY----PENPIAlsaqahlRRFYESFGFIAVSQE 174
Cdd:COG0456    4 LLGLVDGGDEAEIEDLAVDPEYRGRGIGRALLEAALERarergARRLRlevrEDNEAA-------IALYEKLGFEEVGER 76

                         90
                 ....*....|....
gi 502304173 175 YLEDGIPHIDMVRQ 188
Cdd:COG0456   77 PNYYGDDALVMEKE 90

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
                 ....*....|....*....|....*....|....*...
gi 502304173   1 MDVRAAVALQAGKPLEVMAVQLEGPRAGEVPVEVKATG 38
Cdd:cd08278    1 MKTTAAVVREPGGPFVLEDVELDDPRPDEVLVRIVATG 38

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
                 ....*....|....*....|....*....|....*.
gi 502304173   3 VRAAVALQAGKPLEVMAVQLEGPRAGEVPVEVKATG 38
Cdd:cd08279    1 MRAAVLHEVGKPLEIEEVELDDPGPGEVLVRIAAAG 36

N-acetyltransferase, GNAT superfamily (includes histone acetyltransferase HPA2) [Transcription, General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 502304173  79 ELDGKDIDALHLRLLEGAELLGAARiLKPYePQDPSKIGRVVVSPDHRGKRLGDALMSEAIAA-----CERLYPEnpiAL 153
Cdd:COG0454   26 AMEGSLAGAEFIAVDDKGEPIGFAG-LRRL-DDKVLELKRLYVLPEYRGKGIGKALLEALLEWarergCTALELD---TL 100

                         90       100
                 ....*....|....*....|
gi 502304173 154 SAQAHLRRFYESFGFIAVSQ 173
Cdd:COG0454  101 DGNPAAIRFYERLGFKEIER 120

Liver alcohol dehydrogenase and related 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. 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
                 ....*....|....*....|....*....|....*
gi 502304173   4 RAAVALQAGKPLEVMAVQLEGPRAGEVPVEVKATG 38
Cdd:cd05279    2 KAAVLWEKGKPLSIEEIEVAPPKAGEVRIKVVATG 36

Predicted acetyltransferase, GNAT family [General function prediction only];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 502304173 116 IGRVVVSPDHRGKRLGDALMSEAIAACERLYPENPI--ALSAQAHLRRFYESFGFIAV 171
Cdd:COG3393   18 ISGVYTHPEYRGRGLASALVAALAREALARGARTPFlyVDADNPAARRLYERLGFRPV 75

Alcohol dehydrogenases of the MDR 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. 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
                 ....*....|....*....|....*....|....*.
gi 502304173   4 RAAVALQAGKPLEVMAVQLEGPRAGEVPVEVKATGA 39
Cdd:cd08263    2 KAAVLKGPNPPLTIEEIPVPRPKEGEILIRVAACGV 37