3PL1

Determination of the crystal structure of the pyrazinamidase from M.tuberculosis : a structure-function analysis for prediction resistance to pyrazinamide.

Replaces:  3GBC

Summary for 3PL1

• Entry DOI: 10.2210/pdb3pl1/pdb
• Descriptor: PYRAZINAMIDASE/NICOTINAMIDASE PNCA (PZase), FE (II) ION (3 entities in total)
• Functional Keywords: rossmann fold, nicotinamidase-pyrazinamidase, resistance to pyrazinamide, hydrolase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 1
• Total formula weight: 19677.42

Authors

Petrella, S.,Gelus-Ziental, N.,Mayer, C.,Sougakoff, W. (deposition date: 2010-11-12, release date: 2011-01-12, Last modification date: 2023-11-01)

Primary citation

Petrella, S.,Gelus-Ziental, N.,Maudry, A.,Laurans, C.,Boudjelloul, R.,Sougakoff, W.
Crystal Structure of the Pyrazinamidase of Mycobacterium tuberculosis: Insights into Natural and Acquired Resistance to Pyrazinamide.
Plos One, 6:e15785-e15785, 2011

PubMed 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 Fe(2+) 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-Lys96 motif evocating a cysteine-based catalytic mechanism. Mutants have been constructed and investigated by kinetic and thermal shift assays, highlighting the importance of protein folding and thermal stability in the pyrazinamidase activity.

PubMed: 21283666
DOI: 10.1371/journal.pone.0015785

Experimental method

X-RAY DIFFRACTION (2.2 Å)