3P72

structure of platelet Glycoprotein 1b alpha with a bound peptide inhibitor

3P72 の概要

• エントリーDOI: 10.2210/pdb3p72/pdb
• 関連するPDBエントリー: 1GWB 1SQ0 1U0N
• 関連するBIRD辞書のPRD_ID: PRD_000829
• 分子名称: Platelet glycoprotein Ib alpha chain, OS1 peptide, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: leucine-rich repeat, coagulation, inhibitor, blood clotting-inhibitor complex, blood clotting/inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31281.63

構造登録者

McEwan, P.A.,Andrews, R.K.,Emsley, J. (登録日: 2010-10-12, 公開日: 2010-11-24, 最終更新日: 2024-10-30)

主引用文献

McEwan, P.A.,Andrews, R.K.,Emsley, J.
Glycoprotein Ibalpha inhibitor complex structure reveals a combined steric and allosteric mechanism of von Willebrand factor antagonism.
Blood, 114:4883-4885, 2009

PubMed Abstract: Platelet glycoprotein Ibalpha (GpIbalpha) interactions with von Willebrand factor (VWF) are a critical early event in platelet adhesion, which contributes to hemostasis and thrombosis. Here we report the structure of a complex between GpIbalpha and a potent peptide inhibitor. The cyclic peptide (CTERMALHNLC) was isolated from a cysteine-constrained phage display library, and in the complex this forms one and a half turns of an amphipathic alpha-helix, the curvature of which facilitates contacts with the curved concave face of the GpIbalpha leucine-rich repeats. The peptide has only limited overlap with the VWF binding site. It effectively inhibits by stabilizing an alternative alpha-helical conformation of a regulatory loop that forms an extended beta-hairpin upon VWF binding. The structure defines a previously unrecognized binding site within GpIbalpha and represents a clear strategy for developing antiplatelet agents targeting the GpIbalpha-VWF interaction allosterically.

PubMed: 19726719
DOI: 10.1182/blood-2009-05-224170

実験手法

X-RAY DIFFRACTION (1.9 Å)