人巨细胞病毒 DNA 聚合酶的 K 和 P 螺旋区突变导致其对膦甲酸钠的敏感性增加。
Hypersusceptibility of Human Cytomegalovirus to Foscarnet Induced by Mutations in Helices K and P of the Viral DNA Polymerase.
机构信息
Research Center in Infectious Diseases, CHU de Québec-Laval University, Quebec City, Quebec, Canada.
Department of Biochemistry, Microbiology, and Bioinformatics, PROTEO, Laval University, Quebec City, Quebec, Canada.
出版信息
Antimicrob Agents Chemother. 2020 Mar 24;64(4). doi: 10.1128/AAC.01910-19.
Abstract
Herein, we phenotypically and enzymatically characterize the theoretical mutation Q579I in helix K and the already described clinical mutation K805Q in helix P of cytomegalovirus DNA polymerase for susceptibility to foscarnet. Q579I and K805Q recombinant viruses were hypersusceptible to foscarnet (respective mean 50% effective concentrations [EC] of 0.12- and 0.19-fold that of the wild type). Three-dimensional modeling analysis suggested that both mutations favor the closed conformation of the enzyme to which foscarnet binds with a higher affinity.
摘要
在此，我们对巨细胞病毒 DNA 聚合酶螺旋 K 中的理论突变 Q579I 和螺旋 P 中已经描述的临床突变 K805Q 进行表型和酶学特征分析，以确定它们对膦甲酸的敏感性。Q579I 和 K805Q 重组病毒对膦甲酸高度敏感（相对于野生型，分别为 50%有效浓度 [EC] 的 0.12 倍和 0.19 倍）。三维建模分析表明，这两种突变都有利于酶的闭合构象，膦甲酸与该构象具有更高的亲和力。
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