Structure of a novel leech carboxypeptidase inhibitor determined free in solution and in complex with human carboxypeptidase A2

被引：69

作者：

Reverter D. ^{[1
,2
]}

Fernández-Catalán C. ^{[2
]}

Baumgartner R. ^{[2
]}

Pfänder R. ^{[2
]}

Huber R. ^{[2
]}

Bode W. ^{[2
]}

Vendrell J. ^{[1
]}

Holak T.A. ^{[2
]}

Avilés F.X. ^{[1
]}

机构：

[1] Department de Bioquimica I Biologia Molecular, Unitat de Cièndes and Institut de Biologia Fonamental, Universität Autonoma de Barcelona, 08193 Bellaterra, Barcelona

[2] Max Planck Institute for Biochemistry

来源：

Nature Structural Biology | 2000年 / 7卷 / 4期

关键词：

D O I：

10.1038/74092

中图分类号：

学科分类号：

摘要：

Leech carboxypeptidase inhibitor (LCI) is a novel protein inhibitor present in the medicinal leech Hirudo medicinalis. The structures of LCI free and bound to carboxypeptidase A2 (CPA2) have been determined by NMR and X-ray crystallography, respectively. The LCI structure defines a new protein motif that comprises a five-stranded antiparallel β-sheet and one short α-helix. This structure is preserved in the complex with human CPA2 in the X-ray structure, where the contact regions between the inhibitor and the protease are defined. The C-terminal tail of LCl becomes rigid upon binding the protease as shown in the NMR relaxation studies, and it interacts with the carboxypeptidase in a substrate-like manner. The homology between the C- terminal tails of LCl and the potato carboxypeptidase inhibitor represents a striking example of convergent evolution dictated by the target protease. These new structures are of biotechnological interest since they could elucidate the control mechanism of metallo-carboxypeptidases and could be used as lead compounds for the search of fibrinolytic drugs.

引用

页码：322 / 328

页数：6

共 43 条

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