creators_name: Chauhan, Radha
creators_name: Mande, Shekhar C
type: article
datestamp: 2012-01-05 15:13:14
lastmod: 2012-01-05 15:13:14
metadata_visibility: show
title: Site-directed mutagenesis reveals a novel catalytic mechanism of Mycobacterium tuberculosis alkylhydroperoxidase C.
ispublished: pub
subjects: QD
full_text_status: restricted
keywords: antioxidant, dithiothreitol oxidation, glutamine synthetase enzyme, metal-catalysed oxidation
note: Copyright of this article belongs to Portland Press.
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.
date: 2002-10-01
date_type: published
publication: The Biochemical journal
volume: 367
number: Pt 1
publisher: Portland Press
pagerange: 255-61
refereed: TRUE
issn: 0264-6021
official_url: http://www.biochemj.org/bj/367/0255/bj3670255.htm
related_url_url: http://www.biochemj.org/bj/367/0255/bj3670255.htm
related_url_type: pub
citation:   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     
document_url: http://crdd.osdd.net/open/267/1/mande2002.pdf