2hwl
From Proteopedia
(New page: 200px<br /> <applet load="2hwl" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hwl, resolution 2.40Å" /> '''Crystal structure o...) |
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| - | [[Image:2hwl.gif|left|200px]]<br /> | + | [[Image:2hwl.gif|left|200px]]<br /><applet load="2hwl" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2hwl" size=" | + | |
caption="2hwl, resolution 2.40Å" /> | caption="2hwl, resolution 2.40Å" /> | ||
'''Crystal structure of thrombin in complex with fibrinogen gamma' peptide'''<br /> | '''Crystal structure of thrombin in complex with fibrinogen gamma' peptide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Elevated levels of heterodimeric gamma(A)/gamma' fibrinogen 2 have been | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2HWL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG and NA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http:// | + | 2HWL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=NA:'>NA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HWL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
| - | [[Category: Cera, E | + | [[Category: Cera, E Di.]] |
| - | [[Category: Chen, Z | + | [[Category: Chen, Z W.]] |
[[Category: Marino, F.]] | [[Category: Marino, F.]] | ||
| - | [[Category: Mathews, F | + | [[Category: Mathews, F S.]] |
| - | [[Category: Mosesson, M | + | [[Category: Mosesson, M W.]] |
| - | [[Category: Pineda, A | + | [[Category: Pineda, A O.]] |
[[Category: NA]] | [[Category: NA]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: thrombin]] | [[Category: thrombin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:46:32 2008'' |
Revision as of 15:46, 21 February 2008
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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 with and as ligands. Active as Thrombin, with EC number 3.4.21.5 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
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