Mechanistic and functional insights into fatty acid activation in Mycobacterium tuberculosis.
Mechanistic and functional insights into fatty acid activation in Mycobacterium tuberculosis.
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DOI：
10.1038/nchembio.143
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发表时间：
2009-03
影响因子：
14.8
通讯作者：
Gokhale, Rajesh S.
中科院分区：
文献类型：
--
作者：
Arora, Pooja;Goyal, Aneesh;Natarajan, Vivek T.;Rajakumara, Eerappa;Verma, Priyanka;Gupta, Radhika;Yousuf, Malikmohamed;Trivedi, Omita A.;Mohanty, Debasisa;Tyagi, Anil;Sankaranarayanan, Rajan;Gokhale, Rajesh S.
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）中脂肪酰基AMP连接酶（fatty acyl-AMP ligases，FAALs）的发现为脂肪酸激活学说提供了新的视角。这些蛋白质将脂肪酸转化为相应的腺苷酸，腺苷酸是酰基辅酶A合成脂肪酰基辅酶A连接酶（FACL）的中间体。目前，还不清楚专性病原体如结核分枝杆菌如何进化出功能多样性的新主题，以及脂肪酸活化为酰基腺苷酸是否确实是一种一般机制。在这里，基于阐明的FAAL蛋白的第一个结构，并通过产生损失以及获得的功能突变体，相互转换FAAL和FACL活动，我们证明了插入基序决定形成酰基腺苷酸。由于Mtb中的FAAL是毒性脂质生物合成网络中的关键节点，因此针对这些蛋白质的抑制剂提供了同时破坏几种途径的独特多管齐下的方法。
The recent discovery of fatty acyl-AMP ligases (FAALs) in Mycobacterium tuberculosis (Mtb) provided a new perspective to fatty acid activation dogma. These proteins convert fatty acids to corresponding adenylates, which is an intermediate of acyl-CoA-synthesizing fatty acyl-CoA ligases (FACLs). Presently, it is not evident how obligate pathogens like Mtb have evolved such new themes of functional versatility and whether the activation of fatty acids to acyl-adenylates could indeed be a general mechanism. Here, based on elucidation of the first structure of a FAAL protein and by generating loss- as well as gain-of-function mutants that interconvert FAAL and FACL activities, we demonstrate that an insertion motif dictates formation of acyl-adenylate. Since FAALs in Mtb are crucial nodes in biosynthetic network of virulent lipids, inhibitors directed against these proteins provide a unique multi-pronged approach of simultaneously disrupting several pathways.
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影响因子：
15
作者：
Arora, P;Vats, A;Gokhale, RS
通讯作者：
Gokhale, RS
DOI：
10.1073/pnas.0610634104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Jain, Madhulika;Petzold, Christopher J.;Cox, Jeffery S.
通讯作者：
Cox, Jeffery S.
影响因子：
3.1
作者：
Fontan, Patricia;Aris, Virginie;Smith, Issar
通讯作者：
Smith, Issar
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：
Gomez, JE;McKinney, JD
通讯作者：
McKinney, JD