Comment on "urea-mediated protein denaturation: a consensus view".
Comment on "urea-mediated protein denaturation: a consensus view".
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DOI：
10.1021/jp105160a
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发表时间：
2011-02-10
影响因子：
3.3
通讯作者：
Berne, B. J.
中科院分区：
文献类型：
--
作者：
Zhou, Ruhong;Li, Jingyuan;Hua, Lan;Yang, Zaixing;Berne, B. J.
尿素被广泛用作蛋白质变性剂已有一百多年的历史，然而，尽管在过去的几十年里，从实验和理论两个方面进行了广泛的研究，但其化学变性机理仍然存在争议。1R19尿素的变性能力有两种截然不同的机制：“间接”机制和“直接”机制。间接机制表明，尿素通过破坏水结构来变性蛋白质，这反过来又削弱了疏水相互作用，使蛋白质疏水残基不那么紧密，更容易溶解。4另一方面，直接机制表明，尿素通过与蛋白质的直接相互作用来展开蛋白质，无论是通过与主链和/或极性残基的更强的静电相互作用，还是通过优先与蛋白质残基的范德华引力14、15、18。大多数平行研究支持尿素优先结合到蛋白质骨架或侧链10，11，13r15，18的直接机制，尽管最近的一些研究也表明间接机制也可以在尿素诱导的蛋白质变性中发挥作用。8、16、19在之前的一篇论文中，Das和Mukhop adhyay对尿素诱导的蛋白质变性机制提出了一致的观点。16具体地说，Das等人。他们发现，尿素通过与蛋白质的静电相互作用比与水更强的静电作用而优先与泛素结合，更令人惊讶的是，他们发现，当尿素分子从本体移动到蛋白质泛素表面时，它与周围环境的静电能量达到惊人的∼R13千卡/摩尔。这与我们早先对蛋白质溶菌酶的发现相矛盾，在14，21中，我们发现尿素通过其对蛋白质的更强的范德华吸引力来变性蛋白质，当从块体移动到溶菌酶表面时，VDW的能量变化约为R2千卡/摩尔(而水的∼为0千卡/摩尔)。14 Das等人。提出机制上的差异可能是因为它们是不同的蛋白质；即结果可能是蛋白质特有的。经过仔细评估，我们认为这些差异不是来自所使用的不同蛋白质(更多数据见下文)，不能用两项研究中使用的不同截止点和温度来完全解释。Das等人的S结果与我们的不一致最明显地体现在体相和蛋白质第一溶剂化壳层的水静电相互作用能上的巨大差异。在图1中，我们复制了这些水的能量分布曲线。每个水分子与体系其余部分的静电相互作用能约为R20千卡/摩尔
Urea has been widely used as a protein denaturant for more than a hundred years; however, its chemical denaturation mechanism still remains controversial, despite the extensive studies from both experimental and theoretical approaches in last several decades. 1r19 The denaturing power of urea has been explained by two very different mechanisms: the “indirect” and “direct” mechanisms. The indirect mechanism suggests that urea denatures proteins by disrupting the water structure, which in turn weakens the hydrophobic interaction and makes the protein hydrophobic residues less compact and more readily solvated. 4 The direct mechanism, on the other hand, indicates that urea unfolds proteins through direct interactions with protein, either through stronger electrostatic interactions10, 11, 13, 16 with backbone and/or polar residues or through preferential van der Waals attractions14, 15, 18 with protein residues. Most of the concurrent studies support the direct mechanism involving urea’s preferential binding to protein backbone or side chains, 10, 11, 13r15, 18 although some recent studies also indicate that the indirect mechanism can also play a role in the urea-induced protein denaturation. 8, 16, 19In a previous paper, Das and Mukhopadhyay, proposed a consensus view of the urea-induced protein denaturing mechanism. 16 In particular, Das et al. found that urea preferentially binds to ubiquitin through its stronger electrostatic interactions with protein than water, and more surprisingly, they found that when a urea molecule moves from the bulk to the protein ubiquitin surface, it experiences more favorable electrostatic energy with the surrounding environment by an astounding∼ r13 kcal/mol. This contradicts our earlier findings on the protein lysozyme, 14, 21 where we found that urea denatures the protein through its stronger van der Waals attractions to protein than does water, with about a r2 kcal/mol change in vdW energy when moving from the bulk to the lysozyme surface (versus∼ 0 kcal/mol for water). 14 Das et al. proposed that the difference in mechanism might arise because these are different proteins; ie, the results might be protein specific. After a careful evaluation, we believe that the differences are not from the different proteins used (see below for more data) and cannot be fully explained with the different cutoffs and temperatures used in both studies. The disagreement between Das et al.’s results and ours can best be seen in the large difference in the water electrostatic interaction energy for both the bulk and protein first solvation shell (FSS). In Figure 1, we reproduce these energy distribution profiles for water. The electrostatic interaction energy for each water molecule with the rest of the system is about r20 kcal/mol
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影响因子：
3.3
作者：
Das, Atanu;Mukhopadhyay, Chaitali
通讯作者：
Mukhopadhyay, Chaitali
影响因子：
1.3
作者：
Kumar, S.;Huang, C.;Kale, L. V.
通讯作者：
Kale, L. V.
影响因子：
15
作者：
ROBINSON, DR;JENCKS, WP
通讯作者：
JENCKS, WP
影响因子：
3.4
作者：
Stumpe, Martin C.;Grubmueller, Helmut
通讯作者：
Grubmueller, Helmut
DOI：
10.1073/pnas.0701249104
发表时间：
2007-04-03
影响因子：
11.1
作者：
Zhou, Ruhong;Eleftheriou, Maria;Berne, Bruce J.
通讯作者：
Berne, Bruce J.