QM/MM model of the mouse olfactory receptor MOR244-3 validated by site-directed mutagenesis experiments.
QM/MM model of the mouse olfactory receptor MOR244-3 validated by site-directed mutagenesis experiments.
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DOI：
10.1016/j.bpj.2014.07.031
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发表时间：
2014-09
影响因子：
3.4
通讯作者：
Sivakumar Sekharan;M. Z. Ertem;Hanyi Zhuang;E. Block;H. Matsunami;Ruina Zhang;Jennifer N Wei;Yi Pan;V. Batista
中科院分区：
文献类型：
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作者：
Sivakumar Sekharan;M. Z. Ertem;Hanyi Zhuang;E. Block;H. Matsunami;Ruina Zhang;Jennifer N Wei;Yi Pan;V. Batista
由于缺乏X射线结构模型，理解嗅觉受体的结构/功能关系具有挑战性。在这里，我们介绍了小鼠嗅觉受体MOR 244 -3的QM/MM模型，该模型对有机硫气味剂（例如（甲硫基）甲硫醇）有反应。结合位点由与氨基酸残基H105、C109和N2 O2的杂原子结合的铜离子组成。该模型与定点诱变实验和受体激活的生化测量是一致的，从而为进一步研究嗅觉在分子水平上提供了一个有价值的框架。
Understanding structure/function relationships of olfactory receptors is challenging due to the lack of x-ray structural models. Here, we introduce a QM/MM model of the mouse olfactory receptor MOR244-3, responsive to organosulfur odorants such as (methylthio)methanethiol. The binding site consists of a copper ion bound to the heteroatoms of amino-acid residues H105, C109, and N202. The model is consistent with site-directed mutagenesis experiments and biochemical measurements of the receptor activation, and thus provides a valuable framework for further studies of the sense of smell at the molecular level.