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

doi:10.1006/jmbi.1997.1375

Journal of Molecular Biology

Volume 274, Issue 1, 21 November 1997, Pages 16-20

https://doi.org/10.1006/jmbi.1997.1375 Get rights and content

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 Å 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.

Section snippets

Methods

Recombinant human placenta annexin V (Iwasaki et al., 1987) was crystallized as hexagonal crystals of the apo-form with ammonium sulfate as precipitant in the presence of 1 mM calcium chloride as described (Huber et al., 1992). The high-calcium form was prepared by the soaking method, and the final calcium concentration of 50 mM instead of 20 mM (Huber et al., 1992) was reached by stepwise increment of the calcium concentration to avoid destruction of the crystal. The annexin V and K-201

Acknowledgements

We are grateful to Kowa Co., Japan for the gift of recombinant annexin V. We appreciate the discussions and encouragement of Drs K. Iwata, K. Aisaka and T. Yamaki. We thank Dr D. Knighton for proof reading and helpful suggestions. The co-ordinates of the apo, Ca²⁺ and complex-forms of recombinant human annexin V will be deposited with the Brookhaven Protein Data Bank and are available directly from the authors on request until they have been processed and released.

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^☆: Supplementary material for this paper comprising two Figures is available fromDOI:10.1006/jmbi.1997.1375.

¹: Edited by R. Huber

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Journal of Molecular Biology

CommunicationCrystal structure of annexin V with its ligand K-201 as a calcium channel activity inhibitor1☆,

Abstract

Section snippets

Methods

Acknowledgements

J. Mol. Biol.

J. Mol. Biol.

J. Mol. Biol.

Biochim. Biophys. Acta

J. Mol. Biol.

Biochim. Biophys. Acta

J. Mol. Biol.

J. Mol. Biol.

Structure-function analysis of the ion channel selectivity filter in human annexin V

Science

X-PLOR, Version 3.1A System for X-ray Crystallography and NMR

The CCP4 suiteprogram for protein crystallography

Acta Crystallog. sect. D

Rat annexin V crystal structureCa2+-induced conformational changes

Science

The high-resolution crystal structure of human annexin III shows subtle differences with annexin V

Biochemistry

Structure and expression of cDNA for an inhibitor of blood coagulation isolated from human placentaa new lipocortin-like protein

J. Biochem.

Communication
Crystal structure of annexin V with its ligand K-201 as a calcium channel activity inhibitor¹☆,

Rat annexin V crystal structureCa²⁺-induced conformational changes