Structural insights into the design of reversible fluorescent probes for metallo-?-lactamases NDM-1, VIM-2, and IMP-1

被引：2

作者：

Price, Sky ^{[1
]}

Mehta, Radhika ^{[1
]}

Tan, Dominique ^{[1
]}

Hinojosa, Abigail ^{[1
]}

Thomas, Pei W. ^{[2
,3
]}

Cummings, Tawanda ^{[1
]}

Fast, Walter ^{[2
,3
]}

Que, Emily L. ^{[1
]}

机构：

[1] Univ Texas Austin, Dept Chem, 105 24 th St Stop A5300, Austin, TX 78712 USA

[2] Univ Texas Austin, Coll Pharm, Div Chem Biol & Med Chem, Austin, TX 78712 USA

[3] Univ Texas Austin, La Montagne Ctr Infect Dis, Austin, TX 78812 USA

来源：

JOURNAL OF INORGANIC BIOCHEMISTRY | 2022年 / 233卷

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

Antibiotic resistance; Metalloenzyme inhibitor; Fluorescent probe; BETA-LACTAMASE; ANTIMICROBIAL RESISTANCE; CLINICAL ISOLATE; GENE;

D O I：

10.1016/j.jinorgbio.2022.111869

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：

Metallo-beta-lactamases (MBLs) are enzymes that are capable of hydrolyzing most beta-lactam antibiotics and all clinically relevant carbapenems. We developed a library of reversible fluorescent turn-on probes that are designed to directly bind to the dizinc active site of these enzymes and can be used to study their dynamic metalation state and enzyme-inhibitor interactions. Structure-function relationships with regards to inhibitory strength and fluorescence turn-on response were evaluated for three representative MBLs.

引用

页数：7

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