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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1717358104 121 EITSEDTVLLVGSGAYPMTLVQIAKETGARVIGIDIDEEAVRYGQQVIRILAPDAPIEIHQATVSELEGIQNVTHVI 197
Cdd:cd08261   156 GVTAGDTVLVVGAGPIGLGVIQVAKARGARVIVVDIDDERLEFARELGADDTINVGDEDVAARLRELTDGEGADVVI 232

2-polyprenyl-3-methyl-5-hydroxy-6-metoxy-1,4-benzoquinol methylase [Coenzyme transport and metabolism]; 2-polyprenyl-3-methyl-5-hydroxy-6-metoxy-1,4-benzoquinol methylase is part of the Pathway/BioSystem: Ubiquinone biosynthesis

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1717358104 127 TVLLVGSGAYPMTLVqiAKETGARVIGIDIDEEAVRYGQQviriLAPDAPIEIHQATVSELEGIQNVTHVIFSSTVemky 206
Cdd:COG2227    27 RVLDVGCGTGRLALA--LARRGADVTGVDISPEALEIARE----RAAELNVDFVQGDLEDLPLEDGSFDLVICSEV---- 96

                  ....*....
gi 1717358104 207 dileeLYHL 215
Cdd:COG2227    97 -----LEHL 100

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1717358104 121 EITSEDTVLLVGSGAYPMTLVQIAKETGARVIGIDIDEEAVRYGQQVIRILAPDAPIEIHQATVSELEGIQNVTHVI 197
Cdd:cd08261   156 GVTAGDTVLVVGAGPIGLGVIQVAKARGARVIVVDIDDERLEFARELGADDTINVGDEDVAARLRELTDGEGADVVI 232

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1717358104 121 EITSEDTVLLVGSGAYPMTLVQIAKETGARVIGIDIDEE----AVRYGQQVIRILAPDAPIEIHQATVSE 186
Cdd:cd08254   162 EVKPGETVLVIGLGGLGLNAVQIAKAMGAAVIAVDIKEEklelAKELGADEVLNSLDDSPKDKKAAGLGG 231

Cyclopropane fatty-acyl-phospholipid synthase and related methyltransferases [Lipid transport and metabolism];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1717358104 126 DTVLLVGSG--AypmTLVQIAKETGARVIGIDIDEEAVRYGQQVIRILAPDAPIEIHQATVSELEG 189
Cdd:COG2230    53 MRVLDIGCGwgG---LALYLARRYGVRVTGVTLSPEQLEYARERAAEAGLADRVEVRLADYRDLPA 115

S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). There are at least five structurally distinct families of AdoMet-MTases, class I being the largest and most diverse. Within this class enzymes can be classified by different substrate specificities (small molecules, lipids, nucleic acids, etc.) and different target atoms for methylation (nitrogen, oxygen, carbon, sulfur, etc.).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1717358104 132 GSGAYpmtLVQIAKETGARVIGIDIDEEAVRYGQQVIRILAPDaPIEIHQATVSEL--EGIQNVTHVI----FSSTVEMK 205
Cdd:cd02440     8 GTGAL---ALALASGPGARVTGVDISPVALELARKAAAALLAD-NVEVLKGDAEELppEADESFDVIIsdppLHHLVEDL 83

                          90
                  ....*....|....*..
gi 1717358104 206 YDILEELYHLTGHDIVV 222
Cdd:cd02440    84 ARFLEEARRLLKPGGVL 100

D-arabinose 1-dehydrogenase, Zn-dependent alcohol dehydrogenase family [Carbohydrate transport and metabolism];

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1717358104 126 DTVLLVGSGAYPMTLVQIAKETGARVIGIDIDEEA 160
Cdd:COG1064   164 DRVAVIGAGGLGHLAVQIAKALGAEVIAVDRSPEK 198

cyclohexanol reductases, including levodione reductase, classical (c) SDRs; Cyloclohexanol reductases,including (6R)-2,2,6-trimethyl-1,4-cyclohexanedione (levodione) reductase of Corynebacterium aquaticum, catalyze the reversible oxidoreduction of hydroxycyclohexanone derivatives. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (alpha/beta folding pattern with a central beta-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1717358104 125 EDTVLLV---GSGAYPMTLVQIAKEtGARVIGIDIDEEAVRYGQQVIRILAPDAPIEIHQATVSELEGIQN 192
Cdd:cd05330     2 KDKVVLItggGSGLGLATAVRLAKE-GAKLSLVDLNEEGLEAAKAALLEIAPDAEVLLIKADVSDEAQVEA 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1717358104 119 QFEITSEDTVLLVGSGayPMTL--VQIAKETGA-RVIGIDIDEE----AVRYG-QQVIRILAPDAPIEIHQAT 183
Cdd:COG1063   156 RAGVKPGDTVLVIGAG--PIGLlaALAARLAGAaRVIVVDRNPErlelARELGaDAVVNPREEDLVEAVRELT 226