Structural insights into the mechanism of intramolecular proteolysis
Structural insights into the mechanism of intramolecular proteolysis
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DOI：
10.1016/s0092-8674(00)80052-5
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发表时间：
1999-09-03
期刊：
影响因子：
64.5
通讯作者：
Guo, HC
中科院分区：
文献类型：
--
作者：
Xu, QA;Buckley, D;Guo, HC
最近发现包括糖基天冬酰胺酶在内的多种蛋白质可以通过单链前体的自催化肽键重排来激活功能。在这里，我们展示了糖基天冬酰胺酶前体的 1.9 埃晶体结构，它们能够通过 N --> O 酰基移位进行自蛋白水解。几个保守残基在高度紧张的反式肽键构型中的可断裂肽键周围排列。该结构说明了亲核侧链如何攻击紧邻上游主链羰基处的可断裂肽键，并提供了对通过 N --> O 或 N --> S 酰基转移进行肽键裂解的结构基础的理解，该转移被各种分子内自动加工蛋白使用。
A variety of proteins, including glycosylasparaginase, have recently been found to activate functions by self-catalyzed peptide bond rearrangements from single-chain precursors. Here we present the 1.9 Angstrom crystal structures of glycosylasparaginase precursors that are able to autoproteolyze via an N --> O acyl shift. Several conserved residues are aligned around the scissile peptide bond that is in a highly strained trans peptide bond configuration. The structure illustrates how a nucleophilic side chain may attack the scissile peptide bond at the immediate upstream backbone carbonyl and provides an understanding of the structural basis for peptide bond cleavage via an N --> O or N --> S acyl shift that is used by various groups of intramolecular autoprocessing proteins.