Crystal structure of annexin V with its ligand K-201 as a calcium channel activity inhibitor

J Mol Biol. 1997 Nov 21;274(1):16-20. doi: 10.1006/jmbi.1997.1375.

Abstract

The crystal structure of recombinant human annexin V complexed with K-201, an inhibitor of the calcium ion channel activity of annexin V, was solved at 3.0 A by molecular replacement including the apo and high-calcium forms. K-201 was bound at the hinge region cavity formed by the N-terminal strand and domains II, III and IV, at the side opposite the calcium and membrane-binding surface, in an L-shaped conformation. Based on the complex and other annexin structures, K-201 is proposed to restrain the hinge movement of annexin V in an allosteric manner, resulting in the inhibition of calcium movement across the annexin V molecule.

MeSH terms

  • Annexin A5 / chemistry*
  • Annexin A5 / genetics
  • Annexin A5 / metabolism
  • Calcium Channel Blockers / chemistry*
  • Calcium Channels / drug effects*
  • Crystallography, X-Ray
  • Humans
  • Ligands
  • Models, Molecular
  • Protein Binding
  • Recombinant Proteins / chemistry
  • Spectrometry, Fluorescence
  • Thiazepines / chemistry*
  • Thiazepines / metabolism

Substances

  • Annexin A5
  • Calcium Channel Blockers
  • Calcium Channels
  • Ligands
  • Recombinant Proteins
  • Thiazepines
  • K201 compound

Associated data

  • PDB/1AVH