Document Type
Preprint
Publication Date
3-1-2007
Journal / Book Title
Journal of Inorganic Chemistry
Abstract
Mycobacterium tuberculosis catalase-peroxidase (Mtb KatG) is a bifunctional enzyme that possesses both catalase and peroxidase activities and is responsible for the activation of the antituberculosis drug isoniazid. Mtb KatG contains an unusual adduct in its distal heme-pocket that consists of the covalently linked Trp107, Tyr229, and Met255. The KatG(Y229F) mutant lacks this adduct and has decreased steady-state catalase activity and enhanced peroxidase activity. In order to test a potential structural role of the adduct that supports catalase activity, we have used resonance Raman spectroscopy to probe the local heme environment of KatG(Y229F). In comparison to wild-type KatG, resting KatG(Y229F) contains a significant amount of 6-coordinate, low-spin heme and a more planar heme. Resonance Raman spectroscopy of the ferrous-CO complex of KatG(Y229F) suggest a non-linear Fe-CO binding geometry that is less tilted than in wild-type KatG. These data provide evidence that the Met-Tyr-Trp adduct imparts structural stability to the active site of KatG that seems to be important for sustaining catalase activity.
DOI
10.1016/j.jinorgbio.2006.11.004
Montclair State University Digital Commons Citation
Kapetanaki, Sofia M.; Zhao, Xiangbo; Yu, Shengwei; Magliozzo, Richard S.; and Schelvis, Johannes, "Modification of the Active Site of Mycobacterium Tuberculosis KatG after Disruption of the Met-Tyr-Trp Cross-Linked Adduct" (2007). Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works. 200.
https://digitalcommons.montclair.edu/chem-biochem-facpubs/200
Published Citation
Published in final edited form as: J Inorg Biochem. 2007 March ; 101(3): 422–433.