3PMA

2.2 Angstrom crystal structure of the complex between Bovine Thrombin and Sucrose Octasulfate

3PMA の概要

• エントリーDOI: 10.2210/pdb3pma/pdb
• 関連するPDBエントリー: 3PMB
• 関連するBIRD辞書のPRD_ID: PRD_900013
• 分子名称: Thrombin light chain, Thrombin heavy chain, 1,3,4,6-tetra-O-sulfo-beta-D-fructofuranose-(2-1)-2,3,4,6-tetra-O-sulfonato-alpha-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: protease, thrombosis, fibrinolysis, agonist, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Bos taurus (bovine,cow,domestic cattle,domestic cow); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 68896.37

構造登録者

Wright, H.T.,Scarsdale, J.N.,Desai, B.J. (登録日: 2010-11-16, 公開日: 2011-07-20, 最終更新日: 2024-11-20)

主引用文献

Desai, B.J.,Boothello, R.S.,Mehta, A.Y.,Scarsdale, J.N.,Wright, H.T.,Desai, U.R.
Interaction of thrombin with sucrose octasulfate.
Biochemistry, 50:6973-6982, 2011

PubMed Abstract: The serine protease thrombin plays multiple roles in many important physiological processes, especially coagulation, where it functions as both a pro- and anticoagulant. The polyanionic glycosaminoglycan heparin modulates thrombin's activity through binding at exosite II. Sucrose octasulfate (SOS) is often used as a surrogate for heparin, but it is not known whether it is an effective heparin mimic in its interaction with thrombin. We have characterized the interaction of SOS with thrombin in solution and determined a crystal structure of their complex. SOS binds thrombin with a K(d) of ~1.4 μM, comparable to that of the much larger polymeric heparin measured under the same conditions. Nonionic (hydrogen bonding) interactions make a larger contribution to thrombin binding of SOS than to heparin. SOS binding to exosite II inhibits thrombin's catalytic activity with high potency but with low efficacy. Analytical ultracentrifugation shows that bovine and human thrombins are monomers in solution in the presence of SOS, in contrast to their complexes with heparin, which are dimers. In the X-ray crystal structure, two molecules of SOS are bound nonequivalently to exosite II portions of a thrombin dimer, in contrast to the 1:2 stoichiometry of the heparin-thrombin complex, which has a different monomer association mode in the dimer. SOS and heparin binding to exosite II of thrombin differ on both chemical and structural levels and, perhaps most significantly, in thrombin inhibition. These differences may offer paths to the design of more potent exosite II binding, allosteric small molecules as modulators of thrombin function.

PubMed: 21736375
DOI: 10.1021/bi2004526

実験手法

X-RAY DIFFRACTION (2.2 Å)