有哪些信誉好的足球投注网站crystal structure of the pyrazinamidase of mycobacterium tuberculosis insights into natural and acquired resistance to pyrazinamide晶体结构的pyrazinamidase结核分枝杆菌吡嗪酰胺洞察自然和获得性耐药.pdfVIP
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crystal structure of the pyrazinamidase of mycobacterium tuberculosis insights into natural and acquired resistance to pyrazinamide晶体结构的pyrazinamidase结核分枝杆菌吡嗪酰胺洞察自然和获得性耐药
Crystal Structure of the Pyrazinamidase of Mycobacterium tuberculosis: Insights into Natural and Acquired Resistance to Pyrazinamide ´ 1 1,2 1 1,3 Stephanie Petrella , Nathalie Gelus-Ziental , Arnaud Maudry , Caroline Laurans , Rachid Boudjelloul1, Wladimir Sougakoff 1,4* ´ ´ ` ´ ´ ´ ˆ ` ´ 1 UPMC Universite Paris 6, ER 5 (EA1541) Bacteriologie-Hygiene, Faculte de Medecine Pitie-Salpetriere, Paris, France, 2 INSERM, U908 et FRE3249 CNRS, Universite Lille I, ´ ` ´ ˆ ` Villeneuve d’Ascq, France, 3 Equipe Operationnelle d’Hygiene et d’Infectiologie, Centre Hospitalier Victor Provo, Roubaix, France, 4 INSERM, UMRS-872-12 Pitie-Salpetriere, LRMA, Paris, France Abstract Pyrazinamidase (PncA) activates the first-line antituberculous drug pyrazinamide into pyrazinoic acid. The crystal structure of the Mycobacterium tuberculosis PncA protein has been determined, showing significant differences in the substrate binding cavity when compared to the pyrazinamidases from Pyrococcus horikoshii and Acinetobacter baumanii. In M. tuberculosis, this region was found to hold a Fe2+ ion coordinated by one aspartate and three histidines, one of them corresponding to His57 which is replaced by Asp in Mycobacterium bovis, a species naturally resistant to pyrazinamide. The binding cavity also contains a Cys138-Asp8-
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