二酮哌嗪
化学
分子动力学
单体
分子间力
折叠(DSP实现)
立体化学
基质(水族馆)
化学选择性
分子模型
分子
计算化学
催化作用
有机化学
海洋学
电气工程
地质学
工程类
聚合物
作者
Vikram R. Shende,Natalia R Harris,Jacob N Sanders,Sean A. Newmister,Yogan Khatri,Mohammad Movassaghi,Kendall N Houk,David H. Sherman
标识
DOI:10.1002/ange.202210254
摘要
In the biosynthesis of the tryptophan-linked dimeric diketopiperazines (DKPs), cytochromes P450 selectively couple DKP monomers to generate a variety of intricate and isomeric frameworks. To determine the molecular basis for selectivity of these biocatalysts we obtained a high-resolution crystal structure of selective Csp2−N bond forming dimerase, AspB. Overlay of the AspB structure onto C−C and C−N bond forming homolog NzeB revealed no significant structural variance to explain their divergent chemoselectivities. Molecular dynamics (MD) simulations identified a region of NzeB with increased conformational flexibility relative to AspB, and interchange of this region along with a single active site mutation led to a variant that catalyzes exclusive C−N bond formation. MD simulations also suggest that intermolecular C−C or C−N bond formation results from a change in mechanism, supported experimentally through use of a substrate mimic.
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