The pyrrole locus is the major orienting factor in ryanodine binding.
The pyrrole locus is the major orienting factor in ryanodine binding.
复制标题
吡咯位点是兰尼定结合的主要定向因素。
DOI：
10.1021/bi9527294
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Ruest,L
中科院分区：
文献类型：
--
作者：
Welch,W;Sutko,JL;Mitchell,KE;Airey,J;Ruest,L
Ryanodine, a natural product, is a complex modulator of a class of intracellular Ca2+release channels commonly called the ryanodine receptors. Ryanodine analogs can cause the channel to persist in long-lived, subconductance states or, at high ligand concentrations, in closed, nonconducting states. In this paper, we further explore the relationship between structure and ryanodine binding to striated muscle. Ryanodine, 3-epiryanodine, and 10-ryanodine are three structural isomers of ryanodine. The dissociation constants of these compounds were measured using rabbit skeletal muscle ryanodine receptors. Placing the pyrrole carbonyl group at the 3-epi- and 10-positions of ryanodol largely restores the large loss of binding energy observed when ryanodine is hydrolyzed to ryanodol. Comparative molecular field analysis successfully predicts the enhanced binding and indicates that the pyrrole group controls the orientation of ligand binding. We propose that the ryanoids are reorientated in the binding site of the ryanodine receptors such that the pyrrole always occupies the same subsite. By applying this model, the binding constants of other ryanoids are predicted.
