Crystal structure of the pyrazinamidase of Mycobacterium tuberculosis: insights into natural and acquired resistance to pyrazinamide.
Crystal structure of the pyrazinamidase of Mycobacterium tuberculosis: insights into natural and acquired resistance to pyrazinamide.
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DOI：
10.1371/journal.pone.0015785
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发表时间：
2011-01-24
期刊：
影响因子：
3.7
通讯作者：
Sougakoff W
中科院分区：
文献类型：
--
作者：
Petrella S;Gelus-Ziental N;Maudry A;Laurans C;Boudjelloul R;Sougakoff W
吡嗪酰胺酶（PncA）将一线抗结核药物吡嗪酰胺活化为吡嗪酸。结核分枝杆菌PncA蛋白的晶体结构已被确定，显示出显着差异的底物结合腔相比，从Pyrococcus horikoshii和鲍曼不动杆菌的吡嗪酰胺酶。In M.在结核病中，发现该区域含有由一个天冬氨酸和三个组氨酸配位的Fe 2+离子，其中一个对应于牛分枝杆菌（一种天然抗吡嗪酰胺的物种）中被Asp取代的His 57。结合腔还含有Cys 138-Asp 8-Lys 96基序，其引发基于半胱氨酸的催化机制。突变体已被构建和研究的动力学和热位移测定，突出了蛋白质折叠和热稳定性的吡嗪酰胺酶活性的重要性。
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-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.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
4.5
作者：
Pandey, Sushil;Newton, Sandie;Drinkovic, Dragana
通讯作者：
Drinkovic, Dragana
DOI：
10.1107/s0907444904023510
发表时间：
2004-12-01
影响因子：
2.2
作者：
Vagin, AA;Steiner, RA;Murshudov, GN
通讯作者：
Murshudov, GN