Hydrolysis of Chemically Distinct Sites of Human Serum Albumin by Polyoxometalate: A Hybrid QM/MM (ONIOM) Study
Hydrolysis of Chemically Distinct Sites of Human Serum Albumin by Polyoxometalate: A Hybrid QM/MM (ONIOM) Study
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DOI：
10.1002/jcc.25528
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发表时间：
2019-01-05
影响因子：
3
通讯作者：
Prabhakar, Rajeev
中科院分区：
文献类型：
--
作者：
Jayasinghe-Arachchige, Vindi M.;Hu, Qiaoyu;Prabhakar, Rajeev
采用混合双层QM/MM（ONIOM）方法研究了[Zr（OH）（PW 11 O39）]（4-）（ZrK）对人血清白蛋白（HSA）4个不同化学结构的切割位点的水解机理。这些反应已经被提出通过以下两种机制发生：内部攻击（IA）和水辅助（WA）。在这两种机制中，预测HSA的Cys 392-Glu 393位点中的肽键的裂解发生在该机制的限速步骤中。与27.5千卡/摩尔的障碍，该网站的水解，IA机制被发现是积极更有利的WA机制（障碍= 31.6千卡/摩尔）。IA机制的能量学与广泛的二肽裂解的实验测量值一致。这些计算还表明，HSA的所有四个位点的水解具有能量偏好（Cys 392-Glu 393、Ala 257-Asp 258、Lys 313-Asp 314和Arg 114-Leu 115）。(C)2018 Wiley Periodicals，Inc.
In this study, mechanisms of hydrolysis of all four chemically diverse cleavage sites of human serum albumin (HSA) by [Zr(OH) (PW11O39)](4-)(ZrK) have been investigated using the hybrid two-layer QM/MM (ONIOM) method. These reactions have been proposed to occur through the following two mechanisms: internal attack (IA) and water assisted (WA). In both mechanisms, the cleavage of the peptide bond in the Cys392-Glu393 site of HSA is predicted to occur in the rate-limiting step of the mechanism. With the barrier of 27.5 kcal/mol for the hydrolysis of this site, the IA mechanism is found to be energetically more favorable than the WA mechanism (barrier = 31.6 kcal/mol). The energetics for the IA mechanism are in line with the experimentally measured values for the cleavage of a wide range of dipeptides. These calculations also suggest an energetic preference (Cys392-Glu393, Ala257-Asp258, Lys313-Asp314, and Arg114-Leu115) for the hydrolysis of all four sites of HSA. (C) 2018 Wiley Periodicals, Inc.