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
                  ....*....|....*....|....*....|....*....|...
gi 2417000274   1 MVHLLESG-LNLAPIITHQFPIDDYEKGFQTMFSGQSGKVILN 42
Cdd:cd05281   298 VSALLKSGkVDLSPVITHKLPLEDFEEAFELMRSGKCGKVVLY 340

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
                  ....*....|....*....|....*....|....*....|...
gi 2417000274   1 MVHLLESG-LNLAPIITHQFPIDDYEKGFQTMFSGQSGKVILN 42
Cdd:cd05281   298 VSALLKSGkVDLSPVITHKLPLEDFEEAFELMRSGKCGKVVLY 340

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
                  ....*....|....*....|....*....|....*...
gi 2417000274   4 LLESG-LNLAPIITHQFPIDDYEKGFQTMFSGQSGKVI 40
Cdd:cd08234   295 LLESGkIDVKGLVSHRLPLEEVPEALEGMRSGGALKVV 332

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
                  ....*....|....*....|....*....|....*....|...
gi 2417000274   2 VHLLESG-LNLAPIITHQFPIDDYEKGFQTMFSG--QSGKVIL 41
Cdd:cd08236   301 LDLLASGkIKVEPLITHRLPLEDGPAAFERLADReeFSGKVLL 343

L-idonate 5-dehydrogenase; L-idonate 5-dehydrogenase (L-ido 5-DH ) catalyzes the conversion of L-lodonate to 5-ketogluconate in the metabolism of L-Idonate to 6-P-gluconate. In E. coli, this GntII pathway is a subsidiary pathway to the canonical GntI system, which also phosphorylates and transports gluconate. L-ido 5-DH is found in an operon with a regulator indR, transporter idnT, 5-keto-D-gluconate 5-reductase, and Gnt kinase. L-ido 5-DH is a zinc-dependent alcohol dehydrogenase-like protein. The alcohol dehydrogenase ADH-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) which displays 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 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. 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
                  ....*....|....*....|....*....|....*....|..
gi 2417000274   2 VHLLESG-LNLAPIITHQFPIDDYEKGFQTMF-SGQSGKVIL 41
Cdd:cd08232   296 VRLLAAGrIDVRPLITAVFPLEEAAEAFALAAdRTRSVKVQL 337

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
                  ....*....|....*....|....*....|....*....|..
gi 2417000274   2 VHLLESGL-NLAPIITHQFPIDDYEKGFQTMFSGQSG--KVI 40
Cdd:cd05285   299 IELLASGKvDVKPLITHRFPLEDAVEAFETAAKGKKGviKVV 340

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
                  ....*....|....*....|....*....|...
gi 2417000274   9 LNLAPIITHQFPIDDYEKGFQTMFSGQSGKVIL 41
Cdd:cd08299   339 FNLDPLITHTLPFEKINEGFDLLRSGKSIRTVL 371

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
                  ....*....|....*....|....*....|....*....|.
gi 2417000274   4 LLESG-LNLAPIITHQFPIDDYEKGFQTMFSGQSG--KVIL 41
Cdd:cd08261   295 LLESGkVDPEALITHRFPFEDVPEAFDLWEAPPGGviKVLI 335

Liver 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
                  ....*....|....*....|....*....|...
gi 2417000274   9 LNLAPIITHQFPIDDYEKGFQTMFSGQSGKVIL 41
Cdd:cd08277   332 FDLDELITHVLPFEEINKGFDLMKSGECIRTVI 364

NADPH:quinone reductase or related Zn-dependent oxidoreductase [Energy production and conversion, General function prediction only];

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2417000274   1 MVHLLESGlNLAPIITHQFPIDDYEKGFQTMFSGQS-GKVILNWD 44
Cdd:COG0604   279 LARLLAAG-KLRPVIDRVFPLEEAAEAHRLLESGKHrGKVVLTVD 322

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 2417000274   5 LESGLNLAPIITHQFPIDDYEKGFQTMFSGQSGKVILN 42
Cdd:cd08300   331 MKGKIKVDEFITHTMPLDEINEAFDLMHAGKSIRTVVK 368