Structure−Activity Study of New Inhibitors of Human Betaine-Homocysteine S-Methyltransferase
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چکیده
منابع مشابه
Association of betaine-homocysteine S-methyltransferase with microtubules.
In mammals, betaine of the mitochondrial matrix is used in the cytosol by betaine-homocysteine S-methyltransferase for methionine synthesis. The resulting dimethylglycine is shuttled back into the mitochondrial matrix for further degradation. Nanospray tandem mass spectrometry and N-terminal amino acid sequencing of microtubule-associated proteins from rat liver tubulin revealed that betaine-ho...
متن کاملMolecular characterization and analysis of the porcine betaine homocysteine methyltransferase and betaine homocysteine methyltransferase-2 genes.
Betaine homocysteine methyltransferase (BHMT) and BHMT-2 enzymes methylate homocysteine to form methionine using betaine and S-methylmethionine, respectively. These activities are observed only in the liver of adult rodents, but in adult humans and pigs these activities are detected in both the liver and kidney, indicating the pig is a more appropriate model for studying the biochemical and phy...
متن کاملConformation-dependent inactivation of human betaine-homocysteine S-methyltransferase by hydrogen peroxide in vitro.
Betaine-homocysteine S-methyltransferase (BHMT) transfers a methyl group from betaine to Hcy to form DMG (dimethylglycine) and Met. The reaction is ordered Bi Bi; Hcy is the first substrate to bind and Met is the last product off. Using intrinsic tryptophan fluorescence [Castro, Gratson, Evans, Jiracek, Collinsova, Ludwig and Garrow (2004) Biochemistry 43, 5341-5351], it was shown that BHMT exi...
متن کاملInhibition of human betaine-homocysteine methyltransferase expression by S-adenosylmethionine and methylthioadenosine.
BHMT (betaine-homocysteine methyltransferase) remethylates homocysteine to form methionine. SAM (S-adenosylmethionine) inhibits BHMT activity, but whether SAM modulates BHMT gene expression is unknown. Transcriptional regulation of the human BHMT is also unknown. The present study examined regulation of the human BHMT gene by SAM and its metabolite, MTA (5'-methylthioadenosine). To facilitate t...
متن کاملActive-site-mutagenesis study of rat liver betaine-homocysteine S-methyltransferase.
A site-directed-mutagenesis study of putative active-site residues in rat liver betaine-homocysteine S-methyltransferase has been carried out. Identification of these amino acids was based on data derived from a structural model of the enzyme. No alterations in the CD spectra or the gel-filtration chromatography elution pattern were observed with the mutants, thus suggesting no modification in ...
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ژورنال
عنوان ژورنال: Journal of Medicinal Chemistry
سال: 2009
ISSN: 0022-2623,1520-4804
DOI: 10.1021/jm8015798