Capture and quality control mechanisms for adenosine-5'-triphosphate binding.
Capture and quality control mechanisms for adenosine-5'-triphosphate binding.
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DOI：
10.1021/ja308044w
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发表时间：
2013-04-24
影响因子：
15
通讯作者：
Luthey-Schulten, Zaida
中科院分区：
文献类型：
--
作者：
Li, Li;Martinis, Susan A.;Luthey-Schulten, Zaida
核苷酸转移酶超家族成员的催化事件是由ATP在活性位点的毫秒结合引发的。通过对超家族中最大的一个I类氨酰-tRNA合成酶（aaRSs）的代谢动力学模拟，我们计算了ATP选择和结合的自由能景观。诱变研究和荧光光谱法验证了最常见中间状态的鉴定。快速的第一个结合步骤涉及通过对ATP的三磷酸部分起作用的飞投机制捕获的遭遇复合物的形成。在较慢的核苷结合步骤中，HxxH基序中的保守组氨酸通过碱基堆积相互作用使进入的ATP定向，从而导致自由能表面中的深度最小值。该组氨酸的突变显著降低了实验和计算测量的结合亲和力。代谢动力学模拟进一步揭示了合成酶和最可能的超家族的其他成员用于选择ATP而不是其他核苷三磷酸的中间质量控制状态。
The catalytic events in members of the nucleotidylyl transferase superfamily are initiated by a millisecond binding of ATP in the active site. Through metadynamics simulations on a class I aminoacyl-tRNA synthetase (aaRSs), the largest group in the superfamily, we calculate the free energy landscape of ATP selection and binding. Mutagenesis studies and fluorescence spectroscopy validated the identification of the most populated intermediate states. The rapid first binding step involves formation of encounter complexes captured through a fly-casting mechanism that acts up on the triphosphate moiety of ATP. In the slower nucleoside binding step, a conserved histidine in the HxxH motif orients the incoming ATP through base-stacking interactions resulting in a deep minimum in the free energy surface. Mutation of this histidine significantly decreases the binding affinity measured experimentally and computationally. The metadynamics simulations further reveal an intermediate quality control state that the synthetases and most likely other members of the superfamily use to select ATP over other nucleoside triphosphates.
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影响因子：
15
作者：
Gervasio, FL;Laio, A;Parrinello, M
通讯作者：
Parrinello, M
影响因子：
2.9
作者：
Bas, Delphine C.;Rogers, David M.;Jensen, Jan H.
通讯作者：
Jensen, Jan H.
DOI：
10.1073/pnas.1331150100
发表时间：
2003-06-24
影响因子：
11.1
作者：
Amaro, R;Tajkhorshid, E;Luthey-Schulten, Z
通讯作者：
Luthey-Schulten, Z
影响因子：
4.4
作者：
FELLER, SE;ZHANG, YH;BROOKS, BR
通讯作者：
BROOKS, BR
DOI：
10.1073/pnas.0802879105
发表时间：
2008-06-10
影响因子：
11.1
作者：
Colombo, Giorgio;Morra, Giulia;Verkhivker, Gennady
通讯作者：
Verkhivker, Gennady