Site-directed mutagenesis reveals a novel catalytic mechanism of Mycobacterium tuberculosis alkylhydroperoxidase C.
DIR@IMTECH: CSIR-Institute of Microbial Technology
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Title |
Site-directed mutagenesis reveals a novel catalytic mechanism of Mycobacterium tuberculosis alkylhydroperoxidase C.
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Creator |
Chauhan, Radha
Mande, Shekhar C |
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Subject |
QD Chemistry
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Description |
Mycobacterium tuberculosis alkylhydroperoxidase C (AhpC) belongs to the peroxiredoxin family, but unusually contains three cysteine residues in its active site. It is overexpressed in isoniazid-resistant strains of M. tuberculosis. We demonstrate that AhpC is capable of acting as a general antioxidant by protecting a range of substrates including supercoiled DNA. Active-site Cys to Ala mutants show that all three cysteine residues are important for activity. Cys-61 plays a central role in activity and Cys-174 also appears to be crucial. Interestingly, the C174A mutant is inactive, but double mutant C174/176A shows significant revertant activity. Kinetic parameters indicate that the C176A mutant is active, although much less efficient. We suggest that M. tuberculosis AhpC therefore belongs to a novel peroxiredoxin family and might follow a unique disulphide-relay reaction mechanism.
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Publisher |
Portland Press
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Date |
2002-10-01
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://crdd.osdd.net/open/267/1/mande2002.pdf
Chauhan, Radha and Mande, Shekhar C (2002) Site-directed mutagenesis reveals a novel catalytic mechanism of Mycobacterium tuberculosis alkylhydroperoxidase C. The Biochemical journal, 367 (Pt 1). pp. 255-61. ISSN 0264-6021 |
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Relation |
http://www.biochemj.org/bj/367/0255/bj3670255.htm
http://crdd.osdd.net/open/267/ |
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