From the Biophysics Program and.
From the Biophysics Program and
J Biol Chem. 2017 Dec 22;292(51):20818-20833. doi: 10.1074/jbc.RA117.000220. Epub 2017 Oct 27.
The small heme-containing protein cytochrome can facilitate, inhibit, or have no effect on cytochrome P450 catalysis, often in a P450-dependent and substrate-dependent manner that is not well understood. Herein, solution NMR was used to identify residues interacting with different human drug-metabolizing P450 enzymes. NMR results revealed that P450 enzymes bound to either α4-5 (CYP2A6 and CYP2E1) or this region and α2-3 (CYP2D6 and CYP3A4) and suggested variation in the affinity for Mutations of key residues suggest not only that different surfaces are responsible for binding different P450 enzymes, but that these different complexes are relevant to the observed effects on P450 catalysis.
小分子血红素结合蛋白细胞色素可以促进、抑制或对细胞色素 P450 催化没有影响，通常以依赖细胞色素 P450 和底物的方式进行，这一点还不是很清楚。在此，利用溶液 NMR 鉴定与不同人源药物代谢 P450 酶相互作用的 残基。NMR 结果表明，P450 酶与 α4-5（CYP2A6 和 CYP2E1）或该区域和 α2-3（CYP2D6 和 CYP3A4）结合，并提示对 残基的亲和力存在差异。突变关键 残基不仅表明不同的 表面负责结合不同的 P450 酶，而且这些不同的复合物与观察到的对 P450 催化的影响有关。
