Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects on thermal stability and conformation of DNA produced by the monofunctional adducts of chlorodiethylenetriamineplatinum(II) chloride ([Pt(dien)Cl]Cl) have been investigated. Oligodeoxyribonucleotide duplexes of varying lengths (9-20 base pairs) and of varying central trinucleotide sequences were prepared and characterized that contained site-specific and unique N(7)-guanine adducts. Included are adducts at the sequences of d(AGC), d(AGT), d(CGA), d(TGA), d(TGC), and d(TGT). All these monofunctional adducts decrease the melting temperature (Tm) of the duplexes. This destabilization effect exhibits a sequence-dependent variability. The highest lowering of Tm is observed for the modified duplexes containing the central sequence of pyrimidine-guanine-pyrimidine. The destabilization effect is reduced with decreasing concentrations of Na+. Polarography, circular dichroism, phenanthroline-copper, and chemical probes reveal conformational distortions spreading over several base pairs around the adduct. The effects of monofunctional platinum(II) adducts on conformational distortions in DNA exhibit a sequence-dependent variability similar to those on thermal stability of DNA. The influence of the monofunctional adduct formed by cis-diamminemonoaquamonochloroplatinum(II) on the stability of the oligonucleotide duplex has been also studied. This lesion decreases thermal stability of DNA in the same way as does the adduct of [Pt(dien)Cl]Cl.
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PMID:Sequence-dependent distortions induced in DNA by monofunctional platinum(II) binding. 146 26

The reaction of a histidine-containing peptide (angiotensin I) with copper (II)/ascorbate under physiological conditions has been studied chemically. In the presence of a catalytic amount of copper(II) ion, ascorbate mediated the oxidative damage to the peptide via selective loss of the histidine residue. Furthermore, the reaction of copper(II)/ascorbate with the peptide gave two products (AGT-1 and AGT-2) selectively. From amino acid analysis of the modified peptides, it was found that either of the two histidine residues within the native peptide was modified. Amino-terminal sequence analysis indicated that AGT-1 and AGT-2 were modified at the His9 and the His6, respectively. In addition, the data of FAB-MS and 1H NMR suggested that the unknown residues (modified histidine) within AGT-1 and AGT-2 should have the 2-imidazolone structure. In order to confirm the 2-imidazolone residue in both modified peptides, they were hydrolyzed and analyzed by reverse-phase HPLC. The result demonstrated that the acid hydrolysis of modified peptides gave a product which was identical to authentic 2-imidazolone residue. Consequently, it was confirmed that the reaction of Cu(II)/ascorbate occurs specifically at the C-2 position of the imidazole ring of the histidine residue within a peptide.
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PMID:Site-specific oxidation of angiotensin I by copper(II) and L-ascorbate: conversion of histidine residues to 2-imidazolones. 224 Nov 71

Hemochromatosis and Wilson disease (WD), characterized by the excess hepatic deposition of iron and copper, respectively, produce oxidative stress and increase the risk of liver cancer. Because the frequency of p53 mutated alleles in nontumorous human tissue may be a biomarker of oxyradical damage and identify individuals at increased cancer risk, we have determined the frequency of p53 mutated alleles in nontumorous liver tissue from WD and hemochromatosis patients. When compared with the liver samples from normal controls, higher frequencies of G:C to T:A transversions at codon 249 (P < 0.001) and C:G to A:T transversions and C:G to T:A transitions at codon 250 (P < 0.001 and P < 0.005) were found in liver tissue from WD cases, and a higher frequency of G:C to T:A transversions at codon 249 (P < 0.05) also was found in liver tissue from hemochromatosis cases. Sixty percent of the WD and 28% of hemochromatosis cases also showed a higher expression of inducible nitric oxide synthase in the liver, which suggests nitric oxide as a source of increased oxidative stress. A high level of etheno-DNA adducts, formed from oxyradical-induced lipid peroxidation, in liver from WD and hemochromatosis patients has been reported previously. Therefore, we exposed a wild-type p53 TK-6 lymphoblastoid cell line to 4-hydroxynonenal, an unsaturated aldehyde involved in lipid peroxidation, and observed an increase in G to T transversions at p53 codon 249 (AGG to AGT). These results are consistent with the hypothesis that the generation of oxygen/nitrogen species and unsaturated aldehydes from iron and copper overload in hemochromatosis and WD causes mutations in the p53 tumor suppressor gene.
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PMID:Increased p53 mutation load in nontumorous human liver of wilson disease and hemochromatosis: oxyradical overload diseases. 1105 Jan 62