Evidence of a double-lid movement in Pseudomonas aeruginosa lipase: insights from molecular dynamics simulations.
Evidence of a double-lid movement in Pseudomonas aeruginosa lipase: insights from molecular dynamics simulations.
复制标题
铜绿假单胞菌脂肪酶的双盖运动的证据：分子动力学模拟的见解。
DOI：
10.1371/journal.pcbi.0010028
复制
发表时间：
2005-08
影响因子：
4.3
通讯作者：
Pennathur G
中科院分区：
文献类型：
--
作者：
Cherukuvada SL;Seshasayee AS;Raghunathan K;Anishetty S;Pennathur G
铜绿假单胞菌脂肪酶是一种29 kDa的蛋白质，在测定其晶体结构后，推测其具有在残基125和148之间伸展的盖子。在本文中，使用分子动力学模拟，我们提出，存在，除了上述盖子，在这种脂肪酶的第二个盖子。我们进一步表明，第二个盖子，覆盖残基210-222，作为一个触发盖子的运动的第一。我们还研究了疏水性在盖子运动中的作用，并表明两个残基，Phe 214和Ala 217，在盖子运动中发挥重要作用。据我们所知，这是第一次，我们的手稿中描述的类型的双盖运动已提交给科学界。这项工作也阐明了疏水相互作用的动力学，因此，功能，酶的相互作用。脂肪酶在水-油界面上水解长链脂肪酸酯，通过由覆盖活性位点的盖子域的移动介导的界面活化机制。研究眼睑运动是蛋白质动力学领域的一个活跃研究领域。来自铜绿假单胞菌的脂肪酶是一种29 kDa的蛋白质，其先前以开放构象结晶，并且如预期的那样，鉴定出约20个残基的盖亚结构域。在本研究中，作者报告了铜绿假单胞菌脂肪酶的广泛的分子动力学模拟。他们表明，这种蛋白质有两个盖子覆盖底物结合口袋。第一个盖子是从已知的晶体结构中提出的。第二个盖子，一个短得多的盖子，位于面向第一个盖子的装订口袋上。此外，使用位置限制模拟，这些作者表明，第二个盖子的运动实际上可能是第一个盖子运动的触发器，并且这种触发动作是由两个盖子之间的疏水接触驱动的。这项计算研究为实验者更详细地研究这种蛋白质的结构和动力学铺平了道路，以便全面了解耦合子域运动。
Pseudomonas aeruginosa lipase is a 29-kDa protein that, following the determination of its crystal structure, was postulated to have a lid that stretched between residues 125 and 148. In this paper, using molecular dynamics simulations, we propose that there exists, in addition to the above-mentioned lid, a novel second lid in this lipase. We further show that the second lid, covering residues 210–222, acts as a triggering lid for the movement of the first. We also investigate the role of hydrophobicity in the movement of the lids and show that two residues, Phe214 and Ala217, play important roles in lid movement. To our knowledge, this is the first time that a double-lid movement of the type described in our manuscript has been presented to the scientific community. This work also elucidates the interplay of hydrophobic interactions in the dynamics, and hence the function, of an enzyme. Lipases hydrolyse long-chain fatty acid esters at water-oil interfaces through the mechanism of interfacial activation mediated by the movement of a lid subdomain that covers the active site. Studying lid movement is an area of active research in the field of protein dynamics. The lipase from Pseudomonas aeruginosa is a 29-kDa protein that was previously crystallized in the open conformation, and as expected, an approximately 20-residue lid subdomain was identified. In the present study, the authors report extensive molecular dynamics simulations of the P. aeruginosa lipase. They show that this protein has two lids covering the substrate-binding pocket. The first lid is the one proposed from the known crystal structure. The second lid, a much shorter one, lies over the binding pocket facing the first lid. Furthermore, using position-restrained simulations, these authors show that movement of the second lid may actually be a trigger for the movement of the first, and that this triggering action is driven by hydrophobic contacts between the two lids. This computational study paves a way for experimentalists to study the structure and dynamics of this protein in greater detail in order to understand coupled subdomain movements in a comprehensive fashion.
登录
查看更多内容
影响因子：
2.1
作者：
Berto, P;Comménil, P;Dehorter, B
通讯作者：
Dehorter, B
DOI：
10.1093/protein/gzg135
发表时间：
2003-12-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
James, JJ;Lakshmi, BS;Gautam, P
通讯作者：
Gautam, P
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG
影响因子：
6.3
作者：
BERENDSEN, HJC;VANDERSPOEL, D;VANDRUNEN, R
通讯作者：
VANDRUNEN, R
影响因子：
3
作者：
EISENHABER, F;LIJNZAAD, P;SCHARF, M
通讯作者：
SCHARF, M