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

Huntington, JA; Kjellberg, Margareta LU and Stenflo, Johan LU (2003) In Structure 11(2). p.205-215
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Structure
volume
11
issue
2
pages
205 - 215
publisher
Cell Press
external identifiers
  • pmid:12575940
  • wos:000180905000012
  • scopus:0037314019
ISSN
0969-2126
language
English
LU publication?
yes
id
bc326883-1975-4e6a-bbd3-79c1d8fb240c (old id 318373)
alternative location
http://www.structure.org/content/article/abstract?uid=PIIS0969212602009449
date added to LUP
2007-09-13 12:16:45
date last changed
2018-01-07 05:45:57
@article{bc326883-1975-4e6a-bbd3-79c1d8fb240c,
  abstract     = {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.},
  author       = {Huntington, JA and Kjellberg, Margareta and Stenflo, Johan},
  issn         = {0969-2126},
  language     = {eng},
  number       = {2},
  pages        = {205--215},
  publisher    = {Cell Press},
  series       = {Structure},
  title        = {Crystal structure of protein C inhibitor provides insights into hormone binding and heparin activation},
  volume       = {11},
  year         = {2003},
}