1sj2
From Proteopedia
|
Crystal structure of Mycobacterium tuberculosis catalase-peroxidase
Overview
The Mycobacterium tuberculosis catalase-peroxidase is a multifunctional, heme-dependent enzyme that activates the core anti-tuberculosis drug, isoniazid. Numerous studies have been undertaken to elucidate the, enzyme-dependent mechanism of isoniazid activation, and it is well, documented that mutations that reduce activity or inactivate the, catalase-peroxidase lead to increased levels of isoniazid resistance in M., tuberculosis. Interpretation of the catalytic activities and the effects, of mutations upon the action of the enzyme to date have been limited due, to the lack of a three-dimensional structure for this enzyme. In order to, provide a more accurate model of the three-dimensional structure of the M., tuberculosis catalase-peroxidase, we have crystallized the enzyme and now, report its crystal structure refined to 2.4-A resolution. The structure, reveals new information about dimer assembly and provides information, about the location of residues that may play a role in catalysis including, candidates for protein-based radical formation. Modeling and computational, studies suggest that the binding site for isoniazid is located near the, delta-meso heme edge rather than in a surface loop structure as currently, proposed. The availability of a crystal structure for the M. tuberculosis, catalase-peroxidase also permits structural and functional effects of, mutations implicated in causing elevated levels of isoniazid resistance in, clinical isolates to be interpreted with improved confidence.
About this Structure
1SJ2 is a Single protein structure of sequence from Mycobacterium tuberculosis with HEM and GOL as ligands. Active as Catalase, with EC number 1.11.1.6 Full crystallographic information is available from OCA.
Reference
Crystal structure of Mycobacterium tuberculosis catalase-peroxidase., Bertrand T, Eady NA, Jones JN, Jesmin, Nagy JM, Jamart-Gregoire B, Raven EL, Brown KA, J Biol Chem. 2004 Sep 10;279(37):38991-9. Epub 2004 Jul 1. PMID:15231843
Page seeded by OCA on Wed Nov 21 02:24:59 2007
