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

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.

SUBMITTER: Price S

PROVIDER: S-EPMC9216179 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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

Price Sky S Mehta Radhika R Tan Dominique D Hinojosa Abigail A Thomas Pei W PW Cummings Tawanda T Fast Walter W Que Emily L EL

Journal of inorganic biochemistry 20220520

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 ...[more]

PMID: 35653820

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