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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5369
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pubmed:dateCreated |
1998-6-22
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pubmed:abstractText |
Although isoniazid (isonicotinic acid hydrazide, INH) is widely used for the treatment of tuberculosis, its molecular target has remained elusive. In response to INH treatment, saturated hexacosanoic acid (C26:0) accumulated on a 12-kilodalton acyl carrier protein (AcpM) that normally carried mycolic acid precursors as long as C50. A protein species purified from INH-treated Mycobacterium tuberculosis was shown to consist of a covalent complex of INH, AcpM, and a beta-ketoacyl acyl carrier protein synthase, KasA. Amino acid-altering mutations in the KasA protein were identified in INH-resistant patient isolates that lacked other mutations associated with resistance to this drug.
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pubmed:grant |
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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 |
0036-8075
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1607-10
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pubmed:dateRevised |
2009-8-10
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pubmed:meshHeading |
pubmed-meshheading:9616124-3-Oxoacyl-(Acyl-Carrier-Protein) Synthase,
pubmed-meshheading:9616124-Acyl Carrier Protein,
pubmed-meshheading:9616124-Amino Acid Sequence,
pubmed-meshheading:9616124-Antitubercular Agents,
pubmed-meshheading:9616124-Drug Resistance, Microbial,
pubmed-meshheading:9616124-Enzyme Inhibitors,
pubmed-meshheading:9616124-Fatty Acids,
pubmed-meshheading:9616124-Genes, Bacterial,
pubmed-meshheading:9616124-Humans,
pubmed-meshheading:9616124-Isoniazid,
pubmed-meshheading:9616124-Molecular Sequence Data,
pubmed-meshheading:9616124-Molecular Weight,
pubmed-meshheading:9616124-Mutation,
pubmed-meshheading:9616124-Mycobacterium tuberculosis,
pubmed-meshheading:9616124-Mycolic Acids,
pubmed-meshheading:9616124-Tuberculosis,
pubmed-meshheading:9616124-Up-Regulation
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pubmed:year |
1998
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pubmed:articleTitle |
Inhibition of a Mycobacterium tuberculosis beta-ketoacyl ACP synthase by isoniazid.
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pubmed:affiliation |
Tuberculosis Research Unit, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases (NIAID), National Institutes of Health, Hamilton, MT 59840, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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