Crystal structure of protein C inhibitor provides insights into hormone binding and heparin activation
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/318373
- author
- Huntington, JA ; Kjellberg, Margareta LU and Stenflo, Johan LU
- organization
- publishing date
- 2003
- 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
- 2016-04-01 12:05:02
- date last changed
- 2022-05-19 00:51:31
@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}},
url = {{http://www.structure.org/content/article/abstract?uid=PIIS0969212602009449}},
volume = {{11}},
year = {{2003}},
}