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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5204
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pubmed:dateCreated |
1995-4-12
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pubmed:abstractText |
Resistance to isoniazid in Mycobacterium tuberculosis can be mediated by substitution of alanine for serine 94 in the InhA protein, the drug's primary target. InhA was shown to catalyze the beta-nicotinamide adenine dinucleotide (NADH)-specific reduction of 2-trans-enoyl-acyl carrier protein, an essential step in fatty acid elongation. Kinetic analyses suggested that isoniazid resistance is due to a decreased affinity of the mutant protein for NADH. The three-dimensional structures of wild-type and mutant InhA, refined to 2.2 and 2.7 angstroms, respectively, revealed that drug resistance is directly related to a perturbation in the hydrogen-bonding network that stabilizes NADH binding.
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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 |
Mar
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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 |
17
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pubmed:volume |
267
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1638-41
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7886450-Bacterial Proteins,
pubmed-meshheading:7886450-Binding Sites,
pubmed-meshheading:7886450-Computer Graphics,
pubmed-meshheading:7886450-Crystallization,
pubmed-meshheading:7886450-Crystallography, X-Ray,
pubmed-meshheading:7886450-Drug Resistance, Microbial,
pubmed-meshheading:7886450-Hydrogen Bonding,
pubmed-meshheading:7886450-Isoniazid,
pubmed-meshheading:7886450-Models, Molecular,
pubmed-meshheading:7886450-Mycobacterium tuberculosis,
pubmed-meshheading:7886450-NAD,
pubmed-meshheading:7886450-Oxidation-Reduction,
pubmed-meshheading:7886450-Oxidoreductases,
pubmed-meshheading:7886450-Protein Conformation,
pubmed-meshheading:7886450-Protein Folding,
pubmed-meshheading:7886450-Protein Structure, Secondary
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pubmed:year |
1995
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pubmed:articleTitle |
Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis.
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pubmed:affiliation |
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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