Computational, structural, and kinetic evidence that Vibrio vulnificus FrsA is not a cofactor-independent pyruvate decarboxylase.
Computational, structural, and kinetic evidence that Vibrio vulnificus FrsA is not a cofactor-independent pyruvate decarboxylase.
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DOI：
10.1021/bi400093y
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发表时间：
2013-03-19
期刊：
影响因子：
2.9
通讯作者：
Richards, Nigel G. J.
中科院分区：
文献类型：
--
作者：
Kellett, Whitney F.;Brunk, Elizabeth;Desai, Bijoy J.;Fedorov, Alexander A.;Almo, Steven C.;Gerlt, John A.;Rothlisberger, Ursula;Richards, Nigel G. J.
最近报道创伤弧菌中的发酵呼吸开关（FrsA）蛋白可催化不依赖于辅因子的丙酮酸脱羧。我们现在报告 QM/MM 计算，检查结合在 FrsA 假定活性位点内的丙酮酸分子的 C-C 键断裂的能量。这些计算表明，结合底物中 C-C 键断裂的势垒为 28 kcal/mol，这与 25 °C 水中丙酮酸非催化脱羧的估计值相似。与理论预测一致，可以结晶并进行结构表征的重组FrsA蛋白没有检测到丙酮酸脱羧酶活性。这些结果表明，FrsA 作为不依赖于辅因子的丙酮酸脱羧酶的功能注释是不正确的。
The fermentation-respiration switch (FrsA) protein in Vibrio vulnificus was recently reported to catalyze the cofactor-independent decarboxylation of pyruvate. We now report QM/MM calculations that examine the energetics of C-C bond cleavage for a pyruvate molecule bound within the putative active site of FrsA. These calculations suggest that the barrier to C-C bond cleavage in the bound substrate is 28 kcal/mol, which is similar to that estimated for the uncatalyzed decarboxylation of pyruvate in water at 25 °C. In agreement with the theoretical predictions, no pyruvate decarboxylase activity was detected for recombinant FrsA protein that could be crystallized and structurally characterized. These results suggest that the functional annotation of FrsA as a cofactor-independent pyruvate decarboxylase is incorrect.
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影响因子：
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