2hwl
From Proteopedia
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| , resolution 2.40Å | |||||||
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| Ligands: | and | ||||||
| Gene: | F2 (Homo sapiens) | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of thrombin in complex with fibrinogen gamma' peptide
Contents |
Overview
Elevated levels of heterodimeric gamma(A)/gamma' fibrinogen 2 have been associated with an increased incidence of coronary artery disease, whereas a lowered content of gamma' chains is associated with an increased risk of venous thrombosis. Both situations may be related to the unique features of thrombin binding to variant gamma' chains. The gamma' peptide is an anionic fragment that binds thrombin with high affinity without interfering directly with substrate binding. Here we report the crystal structure of thrombin bound to the gamma' peptide, solved at 2.4 A resolution. The complex reveals extensive interactions between thrombin and the gamma' peptide mediated by electrostatic contacts with residues of exosite II and hydrophobic interactions with a pocket in close proximity to the Na(+) binding site. In its binding mode, the gamma' peptide completely overlaps with heparin bound to exosite II. These findings are consistent with functional data and broaden our understanding of how thrombin interacts with fibrinogen at the molecular level.
Disease
Known diseases associated with this structure: Dysfibrinogenemia, gamma type OMIM:[134850], Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypofibrinogenemia, gamma type OMIM:[134850], Hypoprothrombinemia OMIM:[176930], Thrombophilia, dysfibrinogenemic OMIM:[134850]
About this Structure
2HWL is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of thrombin in complex with fibrinogen gamma' peptide., Pineda AO, Chen ZW, Marino F, Mathews FS, Mosesson MW, Di Cera E, Biophys Chem. 2007 Feb;125(2-3):556-9. Epub 2006 Aug 23. PMID:16962697
Page seeded by OCA on Thu Mar 20 17:22:34 2008
