Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.1.1.1 (alcohol dehydrogenase)
9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histidine at position 51 of the class I beta 1 alcohol dehydrogenase (ADH) functions as a general base by indirectly abstracting a proton from the alcohol substrate through a hydrogen-bonded proton relay system. The human class II pi-ADH was reported to be polymorphic, having either Ser or Thr, but not His at position 51. It is unknown whether Ser or Thr51 have a catalytic role in ethanol oxidation with pi-ADH. Accordingly, we expressed and purified recombinant mutants of pi-ADH with Thr, Ser, and His at position 51. At pH 6.5, values for Vmax/Km for ethanol were 0.30, 0.10, and 0.09 min-1 mM-1 for pi 51Thr, pi 51Ser, and pi 51His ADH, respectively. Hence the effects of the substitutions were much less than the 11-fold decrease in Vmax/Km observed for beta 1-ADH when a neutral amino acid (Gln) was substituted for His51. Addition of a buffer base (400 mM glycylglycine) had little effect on Vmax/Km of recombinant pi 51Thr or pi 51Ser ADH, while it increased Vmax/Km for ethanol 7-fold for the beta (1)51 Gln ADH. We conclude that there is no evidence for Thr51 of pi-ADH participating in a proton relay similar to that seen in beta 1-ADH and that a base at position 51 may not be a universal requirement for a functional alcohol dehydrogenase with a moderate efficiency for ethanol oxidation at a physiological pH.
...
PMID:Comparative roles of histidine 51 in human beta 1 beta 1 and threonine 51 in pi pi alcohol dehydrogenases. 820 92

The relationship between the size of the substrate binding pocket and the catalytic reactivities with varied alcohols was studied with the Saccharomyces cerevisiae alcohol dehydrogenase I (ScADH) and compared with the liver enzymes from horse (EqADH, EE isoenzyme) and monkey (MmADH alpha, alpha-isoenzyme). The yeast enzyme is most active with ethanol, and its activity decreases as the size of the alcohol is increased, whereas the activities of the liver enzymes increase with larger alcohols. The substrate pocket in ScADH was enlarged by single substitutions of Thr-48 to Ser (T48S), Trp-57 to Met (W57M), and Trp-93 to Ala (W93A), and a double change, T48S:W93A, and a triple, T48S:W57M:W93A. The T48S enzyme has the same pattern of activity (V/K) as wild-type ScADH for linear primary alcohols. The W57M enzymes have lowered reactivity with primary and secondary alcohols. The W93A and T48S:W93A enzymes resemble MmADH alpha in having an inverted specificity pattern for primary alcohols, being 3- and 10-fold more active on hexanol and 350- and 540-fold less active on ethanol, and are as reactive as the liver enzymes with long chain primary alcohols. The three Ala-93 enzymes also acquired weak activity on branched chain alcohols and cyclohexanol.
...
PMID:Inversion of the substrate specificity of yeast alcohol dehydrogenase. 846 7

Xylitol dehydrogenase encoded by gene XYL2 from Pichia stipitis is a member of the medium-chain alcohol dehydrogenase family, as evidenced by the domain organization and a distant homology (24% residue identity with the human class I gamma 1 alcohol dehydrogenase). Much of a loop structure is missing, like in mammalian sorbitol and prokaryotic threonine dehydrogenases, many additional differences occur, and relationships are closest with the sorbitol dehydrogenase, the equivalence of which in P. stipitis may actually be the xylitol dehydrogenase. A second P. stipitis gene, also cloned and corresponding to a xylitol dehydrogenase, is highly different from XYL2, but encodes an enzyme with structural properties typical of the short-chain dehydrogenase family, which also contains an alcohol dehydrogenase (from Drosophila). Thus, yeast xylitol dehydrogenases, like alcohol and polyol dehydrogenases from other sources, have dual derivations, combining similar enzyme activities in separate protein families. In contrast to the situation with the other enzymes, both forms of xylitol dehydrogenase are present in one organism.
...
PMID:Dual relationships of xylitol and alcohol dehydrogenases in families of two protein types. 850 64

The oxidation of L-threonine to 2-amino-ketobutyrate, as catalyzed by L-threonine dehydrogenase, is the first step in the major pathway for threonine catabolism in both eukaryotes and prokaryotes. Threonine dehydrogenase of E. coli has considerable amino-acid sequence homology with a number of Zn(2+)-containing, medium-chain alcohol dehydrogenases. In order to further explore structure/function interrelationships of E. coli threonine dehydrogenase, 35 alleles of tdh that imparted a no-growth or slow-growth phenotype on appropriate indicator media were isolated after mutagenesis with hydroxylamine. Within this collection, 14 mutants had single amino-acid changes that were divided into 4 groups: (a) amino-acid changes associated with proposed ligands to Zn2+; (b) a substitution of one of several conserved glycine residues; (c) mutations at the substrate or coenzyme binding site; (d) alterations that resulted in a change of charge near the active site. These findings uncover previously unidentified amino-acid residues that are important for threonine dehydrogenase catalysis and also indicate that the three-dimensional structure of tetrameric E. coli threonine dehydrogenase has considerable similarity with the dimeric horse liver alcohol dehydrogenase.
...
PMID:Functional analysis of E. coli threonine dehydrogenase by means of mutant isolation and characterization. 851 4

The major ethanol dehydrogenase of cobra liver was characterized in order to clarify isozyme relationships and functional motifs of the vertebrate enzyme. The cobra protein is a class-I form, most related to one of the isozyme subunits (the a form) in Uromastix (lizard) liver. This positions the isozyme duplication and defines the main-line alternative. The new structure also allows extensive correlations with structure/function relationships for alcohol dehydrogenases in general, of which 38 animal variants (still disregarding strain and allelic differences) now have been characterized. Architectural features are discerned, distinguishing the enzyme at large, the classes, and the functional interactions at the sites of substrate binding and coenzyme binding. Variability is greater at the substrate-binding site, with only one of 13 residues strictly conserved (His67, one of the active-site zinc ligands) but all other residues differing among and frequently within classes. However, many substrate-interacting residues are class preferential and may be used in predictive assignments. Class-I/III differences concern position 48 (typically Ser in class I, Thr in class III), position 93 (Phe versus Tyr), position 141 (branch-chained aliphatic residue versus methionine), position 57 (hydrophobic residue versus Asp), position 115 (Asp versus Arg), position 116 (Leu or Ile versus Val), position 306 (Met or Leu/Ile versus Phe), position 309 (Phe or Leu/Ile versus Val) and position 318 (Val or Ile versus Ala). In contrast, coenzyme binding is more conserved. A characteristic coenzyme-binging motif, covering only a 50-residue stretch, is defined as tVDiK (residues 178, 203, 223, 224, 228; capital letters for residues strictly conserved and small-cases letters for residues nearly so). This motif is class independent and unique to animal alcohol dehydrogenases. Therefore, the novel enzyme structure establishes class-I isozyme relationships, shows characteristic 'constant' residues also in the 'variable' class-I line, and defines residue-specific patterns which may have a predictive value in functional assignments of an increasing number of undefined further forms expected to result from gene projects.
...
PMID:Liver class-I alcohol dehydrogenase isozyme relationships and constant patterns in a variable basic structure. Distinctions from characterization of an ethanol dehydrogenase in cobra, Naja naja. 861 31

Previously, we demonstrated that ABP-1 (arylphorin gene-specific binding protein-1), which is suggested to be the transcriptional activator of the arylphorin gene of Sarcophaga peregrina, is present in NIH-Sape-4 cells, which do not express arylphorin. As well as ABP-1, these cells were found to contain another protein (ABP-2) that probably binds to the same sequence as that to which ABP-1 binds [Adachi, N., Kubo, T., and Natori, S. (1993) J. Biochem. 114, 55-60]. We purified ABP-2 from a nuclear extract of NIH-Sape-4 cells and compared its DNA-binding activity with that of ABP-1. Both ABP-1 and ABP-2 were found to bind to the same sequence in the arylphorin gene with the same affinity and stability, but an ABP-2-specific hypersensitive site was detected by DNase I footprinting analysis. Analyses of proteolytic fragments suggested that both ABP-1 and ABP-2 have Zn fingers showing high similarity with that of AEF-1, a transcriptional repressor of the Drosophila melanogaster alcohol dehydrogenase gene that binds to a sequence very similar to that binding ABP-1 and ABP-2. We isolated a candidate cDNA for ABP-2, and the protein it encoded contained nine Zn fingers and regions rich in alanine, glutamine, serine/threonine, glycine, histidine, and asparagine.
...
PMID:Purification, characterization, and cDNA cloning of ABP-2 (arylphorin gene-specific binding protein-2) that specifically binds to the ABP-1-binding sequence in the arylphorin gene of Sarcophaga peregrina. 901 Jul 76

The effect of long-term 'corn peptide (CP)' ingestion on alcohol metabolism was investigated in stroke-prone spontaneously hypertensive rats (SHR-SP) with alcohol loading. Long-term CP ingestion in the EtOH/CP group did not significantly increase plasma GOT and GPT activities but markedly increased hepatic ADH and ALDH activities. Intragastric CP administration prior to a dose of 1.0 g/kg ethanol significantly lowered the blood ethanol concentration in SHR-SP which had been loaded with ethanol for a long time. Compared with non-loaded SHR-SP (control group), the rats loaded for a long time with ethanol (EtOH group) showed high concentrations of taurine, glycine and histidine in the plasma. The plasma threonine and proline concentrations were significantly elevated by long-term CP ingestion (EtOH/CP group), but the plasma alanine concentration was rather decreased. These results suggest that short- or long-term CP ingestion may enhance the alcohol metabolism within the body because of an increase in ADH and ALDH activities as well as the alleviation of alcohol-related hepatic injury.
...
PMID:Effect of long-term 'corn peptide' ingestion on alcohol metabolism in stroke-prone spontaneously hypertensive rats with alcohol loading. 908 82

The structural determinants of substrate recognition in the human class IV, or sigmasigma, alcohol dehydrogenase (ADH) isoenzyme were examined through x-ray crystallography and site-directed mutagenesis. The crystal structure of sigmasigma ADH complexed with NAD+ and acetate was solved to 3-A resolution. The human beta1beta1 and sigmasigma ADH isoenzymes share 69% sequence identity and exhibit dramatically different kinetic properties. Differences in the amino acids at positions 57, 116, 141, 309, and 317 create a different topology within the sigmasigma substrate-binding pocket, relative to the beta1beta1 isoenzyme. The nicotinamide ring of the NAD(H) molecule, in the sigmasigma structure, appears to be twisted relative to its position in the beta1beta1 isoenzyme. In conjunction with movements of Thr-48 and Phe-93, this twist widens the substrate pocket in the vicinity of the catalytic zinc and may contribute to this isoenzyme's high Km for small substrates. The presence of Met-57, Met-141, and Phe-309 narrow the middle region of the sigmasigma substrate pocket and may explain the substantially decreased Km values with increased chain length of substrates in sigmasigma ADH. The kinetic properties of a mutant sigmasigma enzyme (sigma309L317A) suggest that widening the middle region of the substrate pocket increases Km by weakening the interactions between the enzyme and smaller substrates while not affecting the binding of longer alcohols, such as hexanol and retinol.
...
PMID:X-ray structure of human class IV sigmasigma alcohol dehydrogenase. Structural basis for substrate specificity. 922 21

The alcohol dehydrogenase (ADH) activity and ADH cross reacting material (ADH CRM) were measured and Northern blot analysis was carried to define the function and the regulation mechanism of the Adh gene. This study examined how dietary threonine affects the expression of the Adh gene during development of Drosophila melanogaster. Two wild type strains, one homozygous for Adh(F) and one for Adh(S) from Chunan, Korea were used. The ADH activity and CRMs of the Adh(F) strain were 2.1 times higher than those of Adhs strain, and ADH activity was higher with isopropanol (secondary alcohol) than with ethanol (primary alcohol) as a substrate in both Adh(F) and Adh(S) strains. When the larvae, pupae, newly emerged adults (0-1 day), and adults (5-7 days) of Drosophila melanogaster Adh(F) and Adh(S) strains were fed on a defined low yeast and threonine medium, ADH activity and ADH CRM levels were increased. Northern blot analyses indicated that the production of mRNA of the larvae, young adults (0-1 day), and adults (5-7 days) was increased by dietary threonine. ADH activity and ADH CRM increases in Drosophila melanogaster fed on threonine were as a result of threonine-stimulated alteration in the amount of ADH mRNA. The elevated level of the ADH mRNA transcribed from the proximal and distal promoters of threonine-fed larvae and adults showed that there was an induction.
...
PMID:The effect of dietary threonine on Adh expression during the development of Drosophila melanogaster. 933 91

The coding region of the mitochondrial citrate synthase gene (CIT1) from Saccharomyces cerevisiae was amplified by PCR and cloned into an expression vector (pAL4) downstream of the alcohol dehydrogenase (alcA) promoter of Aspergillus nidulans to yield pALCS1. Transformation of A. nidulans A773 with this construct gave stable transformants, AYC#1 and AYC#2, that were phenotypically stable for several mitotic divisions. Southern blot analysis showed that the CIT1 gene was successfully integrated into the chromosomes of the transformants. Western blot analysis and enzymatic assay for citrate synthase revealed that the integrated yeast gene was subject to inducible expression controlled by alcA promoter, which can be induced by threonine.
...
PMID:Inducible expression of yeast mitochondrial citrate synthase in Aspergillus nidulans. 933 92


<< Previous 1 2 3 4 5 6 7 Next >>

---