3P72

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

Summary for 3P72

• Entry DOI: 10.2210/pdb3p72/pdb
• Related: 1GWB 1SQ0 1U0N
• Related PRD ID: PRD_000829
• Descriptor: Platelet glycoprotein Ib alpha chain, OS1 peptide, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: leucine-rich repeat, coagulation, inhibitor, blood clotting-inhibitor complex, blood clotting/inhibitor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 31281.63

Authors

McEwan, P.A.,Andrews, R.K.,Emsley, J. (deposition date: 2010-10-12, release date: 2010-11-24, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)