Meropenem and chromacef intermediates observed in IMP-25 metallo-β-lactamase-catalyzed hydrolysis

Peter Oelschlaeger; Mahesh Aitha; Hao Yang; Joon S. Kang; Antonia L. Zhang; Eleanor M. Liu; John D. Buynak; Michael W. Crowder

doi:10.1128/AAC.04409-14

Meropenem and chromacef intermediates observed in IMP-25 metallo-β-lactamase-catalyzed hydrolysis

Peter Oelschlaeger^*, Mahesh Aitha, Hao Yang, Joon S. Kang, Antonia L. Zhang, Eleanor M. Liu, John D. Buynak, Michael W. Crowder

^*Corresponding author for this work

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

11 Scopus citations

Abstract

Metallo-β-lactamases inactivate most β-lactam antibacterials, and much attention has been paid to their catalytic mechanism. One issue of controversy has been whether β-lactam hydrolysis generally proceeds through an anionic intermediate bound to the active-site Zn(II) ions or not. The formation of an intermediate has not been shown conclusively in imipenemase (IMP) enzymes to date. Here, we provide evidence that intermediates are formed during the hydrolysis of meropenem and chromacef catalyzed by the variant IMP-25 and, to a lesser degree, IMP-1.

Original language	English (US)
Pages (from-to)	4326-4330
Number of pages	5
Journal	Antimicrobial agents and chemotherapy
Volume	59
Issue number	7
DOIs	https://doi.org/10.1128/AAC.04409-14
State	Published - Jul 1 2015
Externally published	Yes

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1128/AAC.04409-14

Cite this

@article{3bd0f7f415484af8b2cb17f8a80e5e9d,

title = "Meropenem and chromacef intermediates observed in IMP-25 metallo-β-lactamase-catalyzed hydrolysis",

abstract = "Metallo-β-lactamases inactivate most β-lactam antibacterials, and much attention has been paid to their catalytic mechanism. One issue of controversy has been whether β-lactam hydrolysis generally proceeds through an anionic intermediate bound to the active-site Zn(II) ions or not. The formation of an intermediate has not been shown conclusively in imipenemase (IMP) enzymes to date. Here, we provide evidence that intermediates are formed during the hydrolysis of meropenem and chromacef catalyzed by the variant IMP-25 and, to a lesser degree, IMP-1.",

author = "Peter Oelschlaeger and Mahesh Aitha and Hao Yang and Kang, {Joon S.} and Zhang, {Antonia L.} and Liu, {Eleanor M.} and Buynak, {John D.} and Crowder, {Michael W.}",

year = "2015",

month = jul,

day = "1",

doi = "10.1128/AAC.04409-14",

language = "English (US)",

volume = "59",

pages = "4326--4330",

journal = "Antimicrobial agents and chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "7",

}

TY - JOUR

T1 - Meropenem and chromacef intermediates observed in IMP-25 metallo-β-lactamase-catalyzed hydrolysis

AU - Oelschlaeger, Peter

AU - Aitha, Mahesh

AU - Yang, Hao

AU - Kang, Joon S.

AU - Zhang, Antonia L.

AU - Liu, Eleanor M.

AU - Buynak, John D.

AU - Crowder, Michael W.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Metallo-β-lactamases inactivate most β-lactam antibacterials, and much attention has been paid to their catalytic mechanism. One issue of controversy has been whether β-lactam hydrolysis generally proceeds through an anionic intermediate bound to the active-site Zn(II) ions or not. The formation of an intermediate has not been shown conclusively in imipenemase (IMP) enzymes to date. Here, we provide evidence that intermediates are formed during the hydrolysis of meropenem and chromacef catalyzed by the variant IMP-25 and, to a lesser degree, IMP-1.

AB - Metallo-β-lactamases inactivate most β-lactam antibacterials, and much attention has been paid to their catalytic mechanism. One issue of controversy has been whether β-lactam hydrolysis generally proceeds through an anionic intermediate bound to the active-site Zn(II) ions or not. The formation of an intermediate has not been shown conclusively in imipenemase (IMP) enzymes to date. Here, we provide evidence that intermediates are formed during the hydrolysis of meropenem and chromacef catalyzed by the variant IMP-25 and, to a lesser degree, IMP-1.

UR - http://www.scopus.com/inward/record.url?scp=84935916147&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84935916147&partnerID=8YFLogxK

U2 - 10.1128/AAC.04409-14

DO - 10.1128/AAC.04409-14

M3 - Article

C2 - 25918145

AN - SCOPUS:84935916147

SN - 0066-4804

VL - 59

SP - 4326

EP - 4330

JO - Antimicrobial agents and chemotherapy

JF - Antimicrobial agents and chemotherapy

IS - 7

ER -

Meropenem and chromacef intermediates observed in IMP-25 metallo-β-lactamase-catalyzed hydrolysis

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this