1tb6: Difference between revisions
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==Overview== | ==Overview== | ||
The maintenance of normal blood flow depends completely on the inhibition | The maintenance of normal blood flow depends completely on the inhibition of thrombin by antithrombin, a member of the serpin family. Antithrombin circulates at a high concentration, but only becomes capable of efficient thrombin inhibition on interaction with heparin or related glycosaminoglycans. The anticoagulant properties of therapeutic heparin are mediated by its interaction with antithrombin, although the structural basis for this interaction is unclear. Here we present the crystal structure at a resolution of 2.5 A of the ternary complex between antithrombin, thrombin and a heparin mimetic (SR123781). The structure reveals a template mechanism with antithrombin and thrombin bound to the same heparin chain. A notably close contact interface, comprised of extensive active site and exosite interactions, explains, in molecular detail, the basis of the antithrombotic properties of therapeutic heparin. | ||
==Disease== | ==Disease== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
[[Category: Esmon, C | [[Category: Esmon, C T.]] | ||
[[Category: Huntington, J | [[Category: Huntington, J A.]] | ||
[[Category: Johnson, D | [[Category: Johnson, D J.]] | ||
[[Category: Li, W.]] | [[Category: Li, W.]] | ||
[[Category: MPD]] | [[Category: MPD]] | ||
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[[Category: heparin]] | [[Category: heparin]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:11:57 2008'' | ||
Revision as of 16:12, 21 February 2008
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2.5A Crystal Structure of the Antithrombin-Thrombin-Heparin Ternary Complex
OverviewOverview
The maintenance of normal blood flow depends completely on the inhibition of thrombin by antithrombin, a member of the serpin family. Antithrombin circulates at a high concentration, but only becomes capable of efficient thrombin inhibition on interaction with heparin or related glycosaminoglycans. The anticoagulant properties of therapeutic heparin are mediated by its interaction with antithrombin, although the structural basis for this interaction is unclear. Here we present the crystal structure at a resolution of 2.5 A of the ternary complex between antithrombin, thrombin and a heparin mimetic (SR123781). The structure reveals a template mechanism with antithrombin and thrombin bound to the same heparin chain. A notably close contact interface, comprised of extensive active site and exosite interactions, explains, in molecular detail, the basis of the antithrombotic properties of therapeutic heparin.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
1TB6 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.
ReferenceReference
Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin., Li W, Johnson DJ, Esmon CT, Huntington JA, Nat Struct Mol Biol. 2004 Sep;11(9):857-62. Epub 2004 Aug 15. PMID:15311269
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