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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1990-7-26
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pubmed:abstractText |
3-Hydroxy-3-methylglutaryl CoA synthase was shown to be inhibited in a time-dependent, irreversible manner by compounds containing the substituted beta-lactone functionality found in the natural product 1233A. The rate of inactivation (kinact) was found to approach the rate of catalysis (kcat). The inactivation was irreversible over several hours. A related compound lacking the hydroxymethyl substituent on the beta-lactone ring is a reversible inhibitor and is competitive with respect to acetylCoA. The results are consistent with beta-lactone ring opening by the active site Cys to form an enzyme bound thioester.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
169
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
610-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:1972621-Acetates,
pubmed-meshheading:1972621-Animals,
pubmed-meshheading:1972621-Anti-Bacterial Agents,
pubmed-meshheading:1972621-Carcinoma, Hepatocellular,
pubmed-meshheading:1972621-Cell Line,
pubmed-meshheading:1972621-Cholestyramine Resin,
pubmed-meshheading:1972621-Fatty Acids, Unsaturated,
pubmed-meshheading:1972621-Humans,
pubmed-meshheading:1972621-Hydroxymethylglutaryl-CoA Synthase,
pubmed-meshheading:1972621-Kinetics,
pubmed-meshheading:1972621-Lactones,
pubmed-meshheading:1972621-Liver,
pubmed-meshheading:1972621-Liver Neoplasms,
pubmed-meshheading:1972621-Lovastatin,
pubmed-meshheading:1972621-Molecular Structure,
pubmed-meshheading:1972621-Oxo-Acid-Lyases,
pubmed-meshheading:1972621-Rats,
pubmed-meshheading:1972621-Structure-Activity Relationship,
pubmed-meshheading:1972621-Tumor Cells, Cultured
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pubmed:year |
1990
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pubmed:articleTitle |
Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A synthase by antibiotic 1233A and other beta-lactones.
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pubmed:affiliation |
Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
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pubmed:publicationType |
Journal Article
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