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首页> 外文期刊>Acta crystallographica, Section D. Biological crystallography >Catalytically distinct states captured in a crystal lattice: the substrate-bound and scavenger states of acylaminoacyl peptidase and their implications for functionality
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Catalytically distinct states captured in a crystal lattice: the substrate-bound and scavenger states of acylaminoacyl peptidase and their implications for functionality

机译：捕获在晶格中的催化不同状态：酰基氨基酰基肽酶的底物结合状态和清除剂状态及其对功能的影响

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摘要

Acylaminoacyl peptidase (AAP) is an oligopeptidase that only cleaves short peptides or protein segments. In the case of AAP from Aeropyrum pernix (ApAAP), previous studies have led to a model in which the clamshell-like opening and closing of the enzyme provides the means of substrate-size selection. The closed form of the enzyme is catalytically active, while opening deactivates the catalytic triad. The crystallographic results presented here show that the open form of ApAAP is indeed functionally disabled. The obtained crystal structures also reveal that the closed form is penetrable to small ligands: inhibitor added to the pre-formed crystal was able to reach the active site of the rigidified protein, which is only possible through the narrow channel of the propeller domain. Molecular-dynamics simulations investigating the structure of the complexes formed with longer peptide substrates showed that their binding within the large crevice of the closed form of ApAAP leaves the enzyme structure unperturbed; however, their accessing the binding site seems more probable when assisted by opening of the enzyme. Thus, the open form of ApAAP corresponds to a scavenger of possible substrates, the actual cleavage of which only takes place if the enzyme is able to re-close.
机译：酰氨基酰基肽酶（AAP）是仅切割短肽或蛋白质片段的寡肽酶。对于来自Aeropyrum pernix（ApAAP）的AAP，以前的研究已经导致了一种模型，其中酶的蛤壳状打开和关闭提供了底物大小选择的手段。封闭形式的酶具有催化活性，而开放则使催化三联体失活。此处给出的晶体学结果表明，ApaAAP的开放形式确实在功能上被禁用。所获得的晶体结构还揭示了封闭形式对小的配体是可渗透的：添加到预形成的晶体中的抑制剂能够到达刚性蛋白质的活性位点，这只能通过螺旋桨结构域的狭窄通道来实现。分子动力学模拟研究了与更长的肽底物形成的复合物的结构，结果表明它们在封闭形式的ApAAP的大缝隙中的结合使酶的结构不受干扰。但是，在打开酶的协助下，它们进入结合位点的可能性更大。因此，ApAAP的开放形式对应于可能的底物的清除剂，仅当酶能够重新闭合时才发生其实际裂解。

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