3PL1

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

「3GBC」から置き換えられました

3PL1 の概要

• エントリーDOI: 10.2210/pdb3pl1/pdb
• 分子名称: PYRAZINAMIDASE/NICOTINAMIDASE PNCA (PZase), FE (II) ION (3 entities in total)
• 機能のキーワード: rossmann fold, nicotinamidase-pyrazinamidase, resistance to pyrazinamide, hydrolase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19677.42

構造登録者

Petrella, S.,Gelus-Ziental, N.,Mayer, C.,Sougakoff, W. (登録日: 2010-11-12, 公開日: 2011-01-12, 最終更新日: 2023-11-01)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.2 Å)