Site-directed mutagenesis reveals a novel catalytic mechanism of Mycobacterium tuberculosis alkylhydroperoxidase C.

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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Abstract

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.

Item Type:	Article
Additional Information:	Copyright of this article belongs to Portland Press.
Uncontrolled Keywords:	antioxidant, dithiothreitol oxidation, glutamine synthetase enzyme, metal-catalysed oxidation
Subjects:	Q Science > QD Chemistry
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	05 Jan 2012 15:13
Last Modified:	05 Jan 2012 15:13
URI:	http://crdd.osdd.net/open/id/eprint/267

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