Inhibition of Mycobacterium tuberculosis pantothenate synthetase by analogues of the reaction intermediate.
Inhibition of Mycobacterium tuberculosis pantothenate synthetase by analogues of the reaction intermediate.
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DOI：
10.1002/cbic.200800437
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发表时间：
2008-11-03
期刊：
影响因子：
3.2
通讯作者：
Abell, Chris
中科院分区：
文献类型：
--
作者：
Ciulli, Alessio;Scott, Duncan E.;Ando, Michiyo;Reyes, Fernando;Saldanha, S. Adrian;Tuck, Kellie L.;Chirgadze, Dimitri Y.;Blundell, Tom L.;Abell, Chris
结核分枝杆菌（Mycobacterium tuberculosis）是结核病（TB）的病原体，感染了全世界大约20亿人，并且估计其中每年有900万人发展为TB。[1，2]结核病目前是世界上由细菌病原体引起的传染病死亡的主要原因，2006年估计有170万人死亡。[3]由于多重耐药的M。鉴于结核病的严重性和当前抗结核疗法的局限性，迫切需要开发具有新作用模式的安全有效的新药。[4]泛酸（维生素B5）是辅酶A和酰基载体蛋白的重要前体。泛酸的从头生物合成途径存在于许多细菌、真菌和植物中，并且包括由panB、panE、panD和panC编码的四种酶。[5]生物信息学分析已经将该途径确定为抗菌剂的潜在靶点。[6]哺乳动物中每种酶的缺乏进一步表明抑制剂可能是选择性的，副作用的风险降低。重要的是，遗传研究表明，M. panC和panD基因缺陷的结核病未能在小鼠感染模型中建立毒力。[7]本研究对M.结核病，删除了泛CD和卡介苗的主要减毒突变，
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), infects approximately two billion people worldwide, and an estimated nine million of these develop TB each year.[1, 2] TB is currently the leading cause of infectious disease mortality in the world by a bacterial pathogen, and claimed an estimated 1.7 million deaths in 2006.[3] As a result of the increasing manifestation of multiple-drug-resistant strains of M. tuberculosis and of the limitations of the current anti-TB therapies, the development of safe and effective new drugs with novel modes of action is urgently needed.[4]Pantothenate (vitamin B5) is the essential precursor to coenzyme A and acyl carrier proteins. The de novo biosynthetic pathway to pantothenate is present in many bacteria, fungi and plants and comprises four enzymes, encoded by panB, panE, panD and panC.[5] Bioinformatics analyses have identified this pathway as a potential target for antimicrobial agents.[6] The absence of each enzyme in mammals further suggests that inhibitors could be selective with a reduced risk of side effects. Crucially, genetic studies have shown that a pantothenate auxotroph of M. tuberculosis defective in the panC and panD genes fails to establish virulence in a mouse model of infection.[7] An attenuated strain of M. tuberculosis that deletes both panCD and the primary attenuating mutations of the bacille Calmette–
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鉴定针对休眠期分枝杆菌感染的基因靶标。
影响因子：
3.7
作者：
Murphy DJ;Brown JR
通讯作者：
Brown JR
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：
14.8
作者：
Ferreras, JA;Ryu, JS;Quadri, LEN
通讯作者：
Quadri, LEN
影响因子：
3.2
作者：
Tuck, Kellie L.;Saldanha, S. Adrian;Abell, Chris
通讯作者：
Abell, Chris
影响因子：
7.7
作者：
Ciulli, Alessio;Abell, Chris
通讯作者：
Abell, Chris