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Structural basis for efonidipine block of a voltage-gated Ca2+ channel.

Abstract：

:Efonidipine is a dual L-/T- type calcium channel blocker with a slow onset of action and a long lasting effect that exibihits antihypertensive and nephroprotective effects. differs from most other DHPs which can induce reflex tachycardia. Efonidipine reduces blood pressure without decreasing cardiac output and exerts organ-protective effects on the heart and kidney. In order to investigate how efonidipine block voltage-gated Ca2+ channel, we determined the crystal structure of CaVAb in complex with efonidipine at atomic resolution using x-ray crystallography. Our results reveal that efonidipine targets the central cavity of a model voltage-gated calcium channel underneath its selectivity filter and occlude the channel in an inactivated state. Binding of efonidipine does not break down the fourfold symmetry of the quaternary structure and its pore structure. Our work provides the structural basis for efonidipine block of a voltage-gated Ca2+ channel at the molecular level.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Xu F,Xiong W,Huang Y,Shen J,Zhou D,Tang L

doi

10.1016/j.bbrc.2019.03.176

subject

Has Abstract

pub_date

2019-06-04 00:00:00

pages

631-634

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)30577-7

journal_volume

513

pub_type

杂志文章

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