GMP and IMP are competitive inhibitors of CMY-10, an extended-spectrum class C β-lactamase

Jung Hyun Na; Young Jun An; Sun Shin Cha

doi:10.1128/AAC.00098-17

GMP and IMP are competitive inhibitors of CMY-10, an extended-spectrum class C β-lactamase

Jung Hyun Na, Young Jun An, Sun Shin Cha

Department of Chemistry & Nanoscience

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Nucleotides were effective in inhibiting the class C β-lactamase CMY-10. IMP was the most potent competitive inhibitor, with a K_i value of 16.2 μM. The crystal structure of CMY-10 complexed with GMP or IMP revealed that nucleotides fit into the R2 subsite of the active site with a unique vertical binding mode where the phosphate group at one terminus is deeply bound in the subsite and the base at the other terminus faces the solvent.

Original language	English
Article number	e00098
Journal	Antimicrobial Agents and Chemotherapy
Volume	61
Issue number	5
DOIs	https://doi.org/10.1128/AAC.00098-17
State	Published - May 2017

Bibliographical note

Funding Information:
This study was supported by the National Research Foundation of Korea grants (NRF-2015R1A2A2A01004168 and NRF-2015M1A5A1037480) and by a grant from Marine Biotechnology Program (PJT200620) funded by Ministry of Oceans and Fisheries, South Korea

Publisher Copyright:
Copyright © 2017 American Society for Microbiology. All Rights Reserved.

Keywords

Competitive inhibitor
GMP
IMP
β-lactamases

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10.1128/AAC.00098-17

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title = "GMP and IMP are competitive inhibitors of CMY-10, an extended-spectrum class C β-lactamase",

abstract = "Nucleotides were effective in inhibiting the class C β-lactamase CMY-10. IMP was the most potent competitive inhibitor, with a Ki value of 16.2 μM. The crystal structure of CMY-10 complexed with GMP or IMP revealed that nucleotides fit into the R2 subsite of the active site with a unique vertical binding mode where the phosphate group at one terminus is deeply bound in the subsite and the base at the other terminus faces the solvent.",

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AU - An, Young Jun

AU - Cha, Sun Shin

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PY - 2017/5

Y1 - 2017/5

N2 - Nucleotides were effective in inhibiting the class C β-lactamase CMY-10. IMP was the most potent competitive inhibitor, with a Ki value of 16.2 μM. The crystal structure of CMY-10 complexed with GMP or IMP revealed that nucleotides fit into the R2 subsite of the active site with a unique vertical binding mode where the phosphate group at one terminus is deeply bound in the subsite and the base at the other terminus faces the solvent.

AB - Nucleotides were effective in inhibiting the class C β-lactamase CMY-10. IMP was the most potent competitive inhibitor, with a Ki value of 16.2 μM. The crystal structure of CMY-10 complexed with GMP or IMP revealed that nucleotides fit into the R2 subsite of the active site with a unique vertical binding mode where the phosphate group at one terminus is deeply bound in the subsite and the base at the other terminus faces the solvent.

KW - Competitive inhibitor

KW - GMP

KW - IMP

KW - β-lactamases

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SN - 0066-4804

VL - 61

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 5

M1 - e00098

ER -

GMP and IMP are competitive inhibitors of CMY-10, an extended-spectrum class C β-lactamase

Abstract

Bibliographical note

Keywords

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