Essential dynamics of lipase binding sites: The effect of inhibitors of different chain length
Essential dynamics of lipase binding sites: The effect of inhibitors of different chain length
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DOI：
10.1093/protein/10.2.149
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发表时间：
1997-02-01
期刊：
影响因子：
--
通讯作者：
Bywater, R
中科院分区：
文献类型：
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作者：
Peters, GH;vanAalten, DMF;Bywater, R
酶如脂肪酶的生物化学活性通常与酶的结构变化有关，导致与底物的选择性和立体特异性反应。为了研究底物及其链长对酶动力学的影响，我们对天然米黑根毛霉脂肪酶（Rml）和脂肪酶-二烷基磷酸盐复合物进行了分子动力学模拟，其中烷基链的长度范围为2至10个碳原子。在水中进行了模拟，并使用400 ps的轨迹来分析这些系统中的基本运动。我们的结果表明，内部运动的Rml和Rml复合物发生在一个子空间中的只有几个自由度。在连接β-折叠和螺旋的溶剂暴露片段中观察到高柔性。特别地，环区域Gly 35-Lys 50和Thr 57-Asn 63在天然酶中广泛波动。在激活和结合的抑制剂，涉及位移的活性位点环，这些运动被大大抑制。随着抑制剂链长的增加，基本子空间中的波动增加，在链长为10时趋于平稳，这对应于活性位点凹槽的大小。
The biochemical activity of enzymes, such as lipases, is often associated with structural changes in the enzyme resulting in selective and stereospecific reactions with the substrate. To investigate the effect of a substrate and its chain length on the dynamics of the enzyme, we have performed molecular dynamics simulations of the native Rhizomucor miehei lipase (Rml) and lipase-dialkylphosophate complexes, where the length of the alkyl chain ranges from two to 10 carbon atoms. Simulations were performed in water and trajectories of 400 ps were used to analyse the essential motions in these systems. Our results indicate that the internal motions of the Rml and Rml complexes occur in a subspace of only a few degrees of freedom. A high flexibility is observed in solvent-exposed segments, which connect beta-sheets and helices. In particular, loop regions Gly35-Lys50 and Thr57-Asn63 fluctuate extensively in the native enzyme. Upon activation and binding of the inhibitor, involving the displacement of the active site loop, these motions are considerably suppressed. With increasing chain length of the inhibitor, the fluctuations in the essential subspace increase, levelling off at a chain length of 10, which corresponds to the size of the active-site groove.