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Structural Insights into the Design of Reversible Fluorescent Probes for Metallo-β-lactamases NDM-1, VIM-2, and IMP-1

Overview
Journal J Inorg Biochem
Specialty Biochemistry
Date 2022 Jun 2
PMID 35653820
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Abstract

Metallo-β-lactamases (MBLs) are enzymes that are capable of hydrolyzing most β-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.

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References
1.
Poirel L, Dortet L, Bernabeu S, Nordmann P . Genetic features of blaNDM-1-positive Enterobacteriaceae. Antimicrob Agents Chemother. 2011; 55(11):5403-7. PMC: 3195013. DOI: 10.1128/AAC.00585-11. View

2.
Brem J, van Berkel S, Zollman D, Lee S, Gileadi O, McHugh P . Structural Basis of Metallo-β-Lactamase Inhibition by Captopril Stereoisomers. Antimicrob Agents Chemother. 2015; 60(1):142-50. PMC: 4704194. DOI: 10.1128/AAC.01335-15. View

3.
Grant G . The many faces of partial inhibition: Revealing imposters with graphical analysis. Arch Biochem Biophys. 2018; 653:10-23. DOI: 10.1016/j.abb.2018.06.009. View

4.
Kim Y, Cunningham M, Mire J, Tesar C, Sacchettini J, Joachimiak A . NDM-1, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism. FASEB J. 2013; 27(5):1917-27. PMC: 3633820. DOI: 10.1096/fj.12-224014. View

5.
Thurlkill R, Grimsley G, Scholtz J, Pace C . pK values of the ionizable groups of proteins. Protein Sci. 2006; 15(5):1214-8. PMC: 2242523. DOI: 10.1110/ps.051840806. View