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)

The relative susceptibilities of lenticular proteins (alpha, beta and gamma-crystallins) and a number of proteins of non-lenticular origin, to hydroxyl radical-mediated peptide bond cleavage were compared. The non-lenticular proteins (bovine serum albumin, ovalbumin, alcohol dehydrogenase, lysozyme, thyroglobulin, beta-amylase, haemoglobin and carbonic anhydrase) were readily cleaved into acid-soluble fragments following 5 hours treatment with copper ions and hydrogen peroxide. In contrast the crystallins were almost totally unaffected by similar treatment. When alpha-crystallin was pre-treated with acid or cleaved into large fragments with cyanogen bromide it became susceptible to hydroxyl radical attack, yet heating the protein did not diminish its resistance. It is suggested that the resistance of alpha-crystallin to the copper/peroxide-mediated fragmentation may be dependent on the conformation of the protein.
...
PMID:Differences in susceptibility between crystallins and non-lenticular proteins to copper and H2O2-mediated peptide bond cleavage. 175 88

Chlordecone (Kepone), a toxic organochlorine pesticide, undergoes bioreduction to chlordecone alcohol in human liver. This reaction is controlled by a cytosolic enzyme, chlordecone reductase (CDR), which may be of the aldo-keto reductase family of xenobiotic metabolizing enzymes [Molowa et al. (1986) J. Biol. Chem. 261, 12624-12627]. To further investigate the primary structure and expression of CDR, we screened a library of human liver cDNAs cloned in the expression vector lambda gt11 and isolated an 800 bp cDNA that directed synthesis of a fusion protein recognized by polyclonal anti-CDR antibodies. Using this cDNA as a probe, we screened two human liver cDNA libraries and found several 1.2-kb cDNAs which would code for a polypeptide with 308 residues (35.8 kDa). However, a similar full-length cDNA, possibly the transcript of a pseudogene, contained an in-frame nonsense codon. The deduced protein sequence of CDR showed 65% similarity to the primary structure of human liver aldehyde reductase and 66% similarity to the inferred protein sequence of rat lens aldose reductase. A search of GenBank revealed significant nucleotide similarity to a cDNA coding for bovine lung prostaglandin f synthase and to a partial cDNA coding for frog lens rho-crystallin. Southern blot analysis of human genomic DNA displayed between 45 and 65 kilobases of DNA hybridizable to CDR cDNA and demonstrated several restriction fragment length polymorphisms among 26 individuals. Northern blot analysis of RNA from human, gerbil, rabbit, hamster, mouse, and rat livers disclosed hybridization with CDR cDNA only for the first three species.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Isolation and characterization of cloned cDNAs encoding human liver chlordecone reductase. 218 32

Aldehyde reductase [EC 1.1.1.2] and aldose reductase [EC 1.1.1.21] are monomeric NADPH-dependent oxidoreductases having wide substrate specificities for carbonyl compounds. These enzymes are implicated in the development of diabetic complications by catalyzing the reduction of glucose to sorbitol. Enzyme inhibition as a direct pharmacokinetic approach to the prevention of diabetic complications resulting from the hyperglycemia of diabetes has not been effective because of nonspecificity of the inhibitors and some appreciable side effects. To understand the structural and evolutionary relationship of these enzymes, we cloned and sequenced cDNAs coding for aldose and aldehyde reductases from human liver and placental cDNA libraries. Human placental aldose reductase (open reading frame of 316 amino acids) has a 65% identity (identical plus conservative substitutions) to human liver and placental aldehyde reductase (open reading frame of 325 amino acids). The two sequences have significant identity to 2,5-diketogluconic acid reductase from corynebacterium, frog rho-crystallin, and bovine lung prostaglandin F synthase (reductase). Southern hybridization analysis of human genomic DNA indicates a multigene system for aldose reductase, suggesting the existence of additional proteins. Thus, the aldo-keto reductase superfamily of proteins may have a more significant and hitherto not fully appreciated role in general cellular metabolism.
...
PMID:The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. 249 33

The human aldose reductase gene has been cloned by screening a human placental cDNA library with antibodies against bovine lens aldose reductase. The nucleotide sequence of the entire coding region has been determined. The deduced amino acid sequence indicates that the human enzyme is 84% identical to the bovine lens aldose reductase and 85% identical to the rat lens aldose reductase. It is also very similar to the human aldehyde reductase, the bovine prostaglandin F synthase, and to the European common frog rho-crystallin. The deduced amino acid sequence also indicates that maturation of aldose reductase involves removal of the N-terminal methionine.
...
PMID:Cloning and sequence determination of human placental aldose reductase gene. 250 9

Aldose reductase (AR) is implicated in some of the disabling complications of diabetes, including neuropathy, retinopathy and cataracts. Our studies are aimed at further clarifying the role of AR in diabetes and facilitating the design of new classes of potent, specific AR inhibitors by gaining an understanding of the protein structure of AR. To this end, we have determined the complete protein sequence of rat lens AR using cDNA analysis and primer extension of mRNA. By comparing protein sequences, we have found that the structural relatedness (41% to 57%) among the vertebrate proteins, aldose reductase, aldehyde reductase, prostaglandin F synthase and the frog lens protein rho-crystallin can now be extended to prokaryotes by the inclusion of Corynebacterium 2,5-diketo-D-gluconate reductase. This more distantly related protein shares 30-40% identity with the vertebrate enzymes. Sequence alignments reveal that 18% of the amino acids are completely conserved in all members of the superfamily, many of them in clusters, suggesting that they mark important structural features such as the nucleotide binding site and substrate binding site. rho-Crystallin, which is structurally related to this superfamily of NADPH-dependent reductases, does not appear to reduce PGH2, PGD2, xylose or glyceraldehyde to any appreciable extent. It does, however, bind NADPH.
...
PMID:A superfamily of NADPH-dependent reductases in eukaryotes and prokaryotes. 250 40

The action of aldose reductase has been implicated in the etiology of a variety of diabetic complications affecting the visual system. However, very little is known regarding the structure and functional organization of the genes encoding this key enzyme. In the present study, we have isolated and characterized complementary DNA clones encoding bovine lens aldose reductase. Nucleotide sequencing of four independently isolated clones was used to establish a 1154 nucleotide composite cDNA sequence. The cDNA sequence encodes 296 amino acids of the aldose reductase primary structure, and contains an additional 261 nucleotides of apparently untranslated sequence downstream from the coding region. No nucleotide sequence differences were found among the four independently isolated aldose reductase cDNA clones. The aldose reductase amino acid sequence deduced from the cDNA shows high homology to that reported for aldose reductase of the rat lens. Significant similarities are also evident between bovine lens aldose reductase and both human liver aldehyde reductase and frog lens rho-crystallin.
...
PMID:Isolation and characterization of cDNA clones encoding aldose reductase. 251 32

zeta-Crystallin of guinea pig lens is distantly related to the family of zinc-containing alcohol/polyol dehydrogenases. The amino acid residues binding the catalytic zinc atom in the alcohol dehydrogenase are exchanged in zeta-crystallin, explaining lack of known enzyme activity, and those residues binding the noncatalytic zinc in the dehydrogenase are located in a segment absent from the crystallin. Mammalian alcohol dehydrogenase, polyol dehydrogenase, and zeta-crystallin therefore constitute a series of proteins exhibiting successive changes in subunit metal content, from two to one and probably zero zinc atoms, respectively. In common with tetrameric dehydrogenases, the crystallin lacks a loop structure present in the dimeric dehydrogenase. Significantly, the crystallin is tetrameric, and a correlation between extra subunit interactions and lack of the loop segment is indicated. The lacking segment in crystallin is extended, encompassing a second loop in the dehydrogenase. The greatest conservation corresponds to the coenzyme-binding domain of the dehydrogenases, the central parts of which are remarkably similar to those in the crystallin. Glycine is by far the most conserved residue and corresponds to positions at bends in the conformation of the alcohol dehydrogenase. The conservation of the stable parts of the fold, the absence of the loop structure, the lack of the metal atoms, and the presence of only a small proportion of oxidation-sensitive cysteine residues in crystallin (5 versus 15 in the beta 1 dehydrogenase subunit) suggest an increased stability of the lens protein and a derivation from the alcohol dehydrogenase family. This is compatible with the recruitment of stable enzyme structures for lens crystallin functions, with trimming of protein structures through these dehydrogenases or a yet unknown enzyme, and with multiple changes in the dehydrogenase family.
...
PMID:Eye lens zeta-crystallin relationships to the family of "long-chain" alcohol/polyol dehydrogenases. Protein trimming and conservation of stable parts. 267 63

Cloned cDNA sequences specific for prostaglandin F (PGF) synthase have been isolated from a cDNA library of bovine lung mRNA sequences. Nucleotide-sequence analyses of cloned cDNA inserts have revealed that PGF synthase consists of a 969-base pair open reading frame coding for a 323-amino acid polypeptide with a Mr of 36,666. The sequence analysis indicates that bovine lung PGF synthase shows 62% identical plus conservative substitutions compared with human liver aldehyde reductase [Wermuth, B., Omar, A., Forster, A., Francesco, C., Wolf, M., Wartburg, J.P., Bullock, B. & Gabbay, K.H. (1987) in Enzymology and Molecular Biology of Carbonyl Metabolism: Aldehyde Dehydrogenase, Aldo-Keto Reductase, and Alcohol Dehydrogenase, eds. Weiner, H. & Flynn, T.G. (Liss, New York), pp. 297-307], which is similar to PGF synthase in molecular weight and substrate specificity. However, comparison of the amino acid sequence of PGF synthase with the National Biomedical Research Foundation protein data base reveals that the sequences of 225 amino acids from C termini of epsilon-crystallin of the European common frog (Rana temporaria) [Tomarev, S.I., Zinovieva, R.D., Dolgilevich, S.M., Luchin, S.V., Krayev, A.S., Skryabin, K.G. & Gause, G.G. (1984) FEBS Lett. 171, 297-302] and of PGF synthase show 77% identical and conservative substitutions without deletions/additions. The result suggests that European common frog lens epsilon-crystallin is identical to bovine lung PGF synthase.
...
PMID:Structural similarity of bovine lung prostaglandin F synthase to lens epsilon-crystallin of the European common frog. 282 66

The life cycle transformation of the protozoan parasite Leishmania from promastigote to amastigote is accompanied by changes in the level of expression of a number of proteins whose function may be necessary for parasite survival in the sandfly vector or mammalian host. To genetically characterize these proteins, we have cloned and characterized cDNA sequences that vary in abundance during the life cycle of Leishmania major. One sequence (P100/11E) encodes a poly(A+) RNA whose abundance is markedly elevated in promastigotes of L. major. The DNA sequence of the P100/11E cDNA predicts an acidic polypeptide of Mr = 32,000 which shows 40-46% similarity to the superfamily of reductase proteins including 2,5-diketo-D-gluconic acid reductase, aldose reductase, aldehyde reductase, and rho-crystallin. The P100/11E sequence of L. major contains the IPKS motif located at the active site of both aldose and aldehyde reductases. The P100/11H sequence was expressed in Escherichia coli, and the purified polypeptide was used to raise rabbit antisera which detect a protein of Mr = 35,000 in promastigotes of L. major. These results provide direct genetic evidence that L. major expresses a sequence homologous to the reductase superfamily as a developmentally regulated gene product in promastigotes.
...
PMID:The developmentally regulated P100/11E gene of Leishmania major shows homology to a superfamily of reductase genes. 291

Aldose reductase (EC 1.1.1.21) has been implicated in a variety of diabetic complications. Here we present the first primary sequence data for the rat lens enzyme, obtained by amino acid and cDNA analysis. We have found structural similarities with another NADPH-dependent oxidoreductase: human liver aldehyde reductase (EC 1.1.1.2). The identity between these two enzymes is 50%. Both enzymes share approx. 40-50% homology with p-crystallin, a major lens protein present only in the frog, Rana pipiens. We propose that aldose reductase, aldehyde reductase and p-crystallin are members of a superfamily of related proteins.
...
PMID:Aldose reductase and p-crystallin belong to the same protein superfamily as aldehyde reductase. 311 86


1 2 3 4 5 6 7 8 Next >>

---