通过晶体学观察到的配体结合对蛋白质构象异构体的选择。
Protein conformer selection by ligand binding observed with crystallography.
作者信息
Cao Y, Musah R A, Wilcox S K, Goodin D B, McRee D E
机构信息
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
出版信息
Protein Sci. 1998 Jan;7(1):72-8. doi: 10.1002/pro.5560070107.
Abstract
A large-scale movement between "closed" and "open" conformations of a protein loop was observed directly with protein crystallography by trapping individual conformers through binding of an exogenous ligand and characterization with solution kinetics. The buried indole ring of Trp191 in cytochrome c peroxidase (CCP) was displaced by exogenous ligands, causing a conformational change of loop Pro190-Asn195 and exposing Trp191 to the protein surface. Kinetic measurements are consistent with a two-step binding mechanism in which the rate-limiting step is a transition of the protein to the open state, which then binds the ligand. This large-scale conformational change of a functionally important region of CCP is independent of ligand and indicates that about 4% of the wild-type protein is in the open form in solution at any given time.
摘要
通过结合外源性配体捕获单个构象异构体，并利用溶液动力学进行表征，利用蛋白质晶体学直接观察到蛋白质环在“封闭”和“开放”构象之间的大规模运动。细胞色素c过氧化物酶（CCP）中Trp191的埋藏吲哚环被外源性配体取代，导致Pro190-Asn195环的构象变化，并使Trp191暴露于蛋白质表面。动力学测量结果与两步结合机制一致，其中限速步骤是蛋白质向开放状态的转变，然后与配体结合。CCP功能重要区域的这种大规模构象变化与配体无关，表明在任何给定时间，约4%的野生型蛋白质在溶液中呈开放形式。
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本文引用的文献
1
Structure of a protein photocycle intermediate by millisecond time-resolved crystallography.通过毫秒级时间分辨晶体学解析蛋白质光循环中间体的结构
Science. 1997 Mar 7;275(5305):1471-5. doi: 10.1126/science.275.5305.1471.
2
Access of ligands to cavities within the core of a protein is rapid.
Nat Struct Biol. 1996 Jun;3(6):516-21. doi: 10.1038/nsb0696-516.
3
Crystal structure of liganded and unliganded forms of bovine plasma retinol-binding protein.牛血浆视黄醇结合蛋白配体结合形式与非配体结合形式的晶体结构。
J Biol Chem. 1993 May 25;268(15):10728-38.
4
Comprehensive explanation of the anomalous EPR spectra of wild-type and mutant cytochrome c peroxidase compound ES.野生型和突变型细胞色素c过氧化物酶化合物ES异常电子顺磁共振光谱的综合解释。
Biochemistry. 1993 Apr 27;32(16):4430-43. doi: 10.1021/bi00067a036.
5
6
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7
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Structure. 1994 Mar 15;2(3):201-8. doi: 10.1016/s0969-2126(00)00021-6.
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9
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Nat Struct Biol. 1994 Aug;1(8):524-31. doi: 10.1038/nsb0894-524.
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