Crystal structure of protein C inhibitor provides insights into hormone binding and heparin activation

被引:38
作者
Huntington, JA
Kjellberg, M
Stenflo, J
机构
[1] Univ Cambridge, Inst Med Res, Dept Haematol, Div Struct Med, Cambridge CB2 2XY, England
[2] Lund Univ, Univ Hosp, Dept Clin Chem, S-20502 Malmo, Sweden
基金
英国医学研究理事会;
关键词
D O I
10.1016/S0969-2126(02)00944-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein C inhibitor (PCI) is a member of the serpin family that has many biological functions. In blood it acts as a procoagulant, and, in the seminal vesicles, it is required for spermatogenesis. The activity of PCI is affected by heparin binding in a manner unique among the heparin binding serpins, and, in addition, PCI binds hydrophobic hormones with apparent specificity for retinoids. Here we present the 2.4 Angstrom crystallographic structure of reactive center loop (RCL) cleaved PCI. A striking feature of the structure is a two-turn N-terminal shortening of helix A, which creates a large hydrophobic pocket that docking studies indicate to be the retinoid binding site. On the basis of surface electrostatic properties, a novel mechanism for heparin activation is proposed.
引用
收藏
页码:205 / 215
页数:11
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