Structural insights into inhibition of the drug target dihydroorotate dehydrogenase by bacterial hydroxyalkylquinolines

被引：6
作者：
Horwitz, Samantha M. [1 ]
Blue, Tamra C. [1 ]
Ambarian, Joseph A. [1 ]
Hoshino, Shotaro [2 ]
Seyedsayamdost, Mohammad R. [2 ]
Davis, Katherine M. [1 ]
机构：
[1] Emory Univ, Dept Chem, Atlanta, GA 30322 USA
[2] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA
来源：
RSC CHEMICAL BIOLOGY | 2022年 / 3卷 / 04期
基金：
美国国家卫生研究院;
关键词：
NATURAL-PRODUCTS; BURKHOLDERIA-PSEUDOMALLEI; FLAVIN REDUCTION; BINDING; REVEALS; IDENTIFICATION; DERIVATIVES; RESISTANCE; MECHANISM; DESIGN;
D O I：
10.1039/d1cb00255d
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Hydroxyalkylquinolines (HAQs) are ubiquitious natural products but their interactions with associated protein targets remain elusive. We report X-ray crystal structures of two HAQs in complex with dihydroorotate dehydrogenase (DHODH). Our results reveal the structural basis of DHODH inhibition by HAQs and open the door to downstream structure-activity relationship studies.
引用
收藏
页码：420 / 425
页数：6
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