Mycobacterium tuberculosis catalase-peroxidase

Bertrand T, NAJ Eady, IN Jones, Jesmin, JM Nagy, B Jamart-Gregoire, EL Raven, KA Brown (2004) Crystal structure of Mycobacterium tuberculosis catalase-peroxidase. J Biol Chem 279 38991-38999. 

Zhao X, S Girotto, S Yu, RS Magliozzo (2004) Evidence for radical formation at Tyr-353 in Mycobacterium tuberculosis catalase-peroxidase (KatG) J Biol Chem 279 7606-7612. 

Z. Zhang, S. Chouchane, R.S. Magliozzo, and J.F. Rusling, Direct voltammetry and catalysis with Mycobacterium tuberculosis catalase-peroxidase, peroxidases, and catalase in lipid films. Anal. Chem. 74,163-170 (2002). 

Ghiladi RA, Rnudsen GM, Medzihradszky KF et al (2005) The Met-Tyr-Trp crosslink in Mycobacterium tuberculosis catalase-peroxidase (KatG) Autocatalytic formation and effect on enzyme catalysis and spectroscopic properties. J Biol Chem 280 22651-22663... 

Suarez J, Ranguelova K, Jarzecki AA et al (2009) An oxyferrous heme/protein-based radical intermediate is catalytically competent in the catalase reaction of Mycobacterium tuberculosis catalase-peroxidase (KatG). J Biol Chem 284 7017-7029... 

Wei, C.J., Lei, B., Musser, J.M., and Tu, S.C. (2003) Isoniazid activation defects in recombinant Mycobacterium tuberculosis catalase-peroxidase (KatG) mutants evident in InhA inhibitor production. Antimicrob. Agents. Chemother. 47, 670-675. 

The peroxidase reaction is coupled with the formation of free radicals, either directly at the protein backbone or at the porphyrin moiety or both. This topic is borderline to the scope of this review and we will restrict ourselves to those studies which have at least a strong connection with the heme iron situation. We mention however, some relevant articles which have appeared in the period reviewed. Specific interest was given to a bi-functional enzyme from Mycobacterium tuberculosis which has both catalase and peroxidase activity.286-287,288-289 We also mention that a critical role of cations like Ca2+ and K+ has been described.290-291... 

Jakopitsch C, Vlasits J, Wiseman B et al (2007) Redox intermediates in the catalase cycle of catalase-peroxidases from Synechocystis PCC 6803, Burkholderia pseudomallei, and Mycobacterium tuberculosis. Biochemistry 46 1183-1193... 

Quemard A, Dessen A, Sugantino M, Jacobs MR Jr, Sacchettini JC, Blanchard JS. Binding of catalase-peroxidase-activated isoniazid to wild-type and mutant Mycobacterium tuberculosis enoyl-ACP reductases. J. Am. Chem. Soc. 1996 118 1561-1562. 

Musser JM, Kapur V, Wilhams DL, Kreiswirth BN, van Soolingen D, van Embden JD. Characterization of the catalase-peroxidase gene (katG) and inhA locus in isoniazid-resistant and -susceptible strains of Mycobacterium tuberculosis by automated DNA sequencing restricted array of mutatins associated with drag re- 45. sistance. J. Infect. Dis. 1996 173 196-202. 

One striking example is the Mycobacterium tuberculosis enoyl-acyl carrier protein (AGP) reductase (InhA), which catalyzes the last reaction in fatty acid elongation. This enzyme is the target of isoniazid, one of the major drugs used for treatment of tuberculosis. Isoniazid is activated by KatG, a mycobacterial catalase—peroxidase, to a species that reacts with the NAD coenzyme of InhA. The resulting adduct is a potent inhibitor of InhA. Efforts are under way to make more potent inhibitors that do not require KatG activation. 

Zhang, Y., Heym, B., Allen, B., Young, D., Cole, S., 1992. The catalase-peroxidase gene and isoniazid resistance of mycobacterium tuberculosis. Nature 358 (6387), 591—593. Available from http //dx.doi.org/10.1038/358591a0. 

The same compounds inhibited the reaction of Mycobacterium tuberculosis peroxidase-catalase with hydrogen peroxide, and hyroxylamine was found to be a weak substrate for this enzyme (Brimnes et al. 1999). 

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