Crystal structure of annexin V with its ligand K-201 as a calcium channel activity inhibitor.
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.
Kaneko
N
N
Department of Cardiology, Tokyo Women's Medical College, Japan.
Ago
H
H
Matsuda
R
R
Inagaki
E
E
Miyano
M
M
D017304:Annexin A5 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry*; D015220:Calcium Channels / Q000187:drug effects*; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013841:Thiazepines / Q000737:chemistry* / Q000378:metabolism
D017304:Annexin A5; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008024:Ligands; D011994:Recombinant Proteins; D013841:Thiazepines; C109183:K201 compound