Related Experiment Video

Updated: Aug 8, 2026

A Platform of Anti-biofilm Assays Suited to the Exploration of Natural Compound Libraries
09:39

A Platform of Anti-biofilm Assays Suited to the Exploration of Natural Compound Libraries

Published on: December 27, 2016

Structural basis for imipenem inhibition of class C beta-lactamases

Beth M Beadle1, Brian K Shoichet

  • 1Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, Illinois 60611-3008, USA.

Antimicrobial Agents and Chemotherapy
|November 19, 2002
PubMed

Insights

Imipenem

Area of Science:

  • Biochemistry
  • Structural Biology
  • Microbiology

Background:

  • Class C beta-lactamase AmpC is a key enzyme conferring bacterial resistance to beta-lactam antibiotics.
  • Understanding the inhibition mechanism of AmpC is crucial for developing new antibiotics.
  • Imipenem is a potent beta-lactam antibiotic often used to treat infections caused by resistant bacteria.

Purpose of the Study:

  • To elucidate the structural basis of imipenem inhibition of the class C beta-lactamase AmpC.
  • To determine the X-ray crystal structure of the imipenem-AmpC acyl-enzyme complex.

Main Methods:

  • X-ray crystallography was employed to determine the structure of the acyl-enzyme complex.
  • The structure was resolved to a resolution of 1.80 Angstroms.

Main Results:

  • The lactam carbonyl oxygen of imipenem was observed to flip by approximately 180 degrees in the AmpC active site.
  • This conformational change displaces the electrophilic acyl center from the site of hydrolytic attack.
  • The observed imipenem-AmpC conformation differs from the moxalactam-AmpC complex structure.

Conclusions:

  • Imipenem inhibits AmpC via a unique conformational change that prevents hydrolysis.
  • The structural findings provide insights into the differential inhibition of beta-lactamases by various antibiotics.
  • This study contributes to the rational design of novel beta-lactamase inhibitors.

More Related Videos

The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions08:06

The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions

Published on: February 1, 2018

Identification of Antibacterial Immunity Proteins in Escherichia coli using MALDI-TOF-TOF-MS/MS and Top-Down Proteomic Analysis09:26

Identification of Antibacterial Immunity Proteins in Escherichia coli using MALDI-TOF-TOF-MS/MS and Top-Down Proteomic Analysis

Published on: May 23, 2021

Related Concept Videos

Bacterial Cell Wall01:22

Bacterial Cell Wall

The bacterial cell wall is an essential structural component that encases the plasma membrane, preserving cellular integrity, determining shape, and protecting against osmotic stress. This rigid yet flexible structure primarily comprises peptidoglycan, a polymer that forms a mesh-like matrix conferring mechanical strength and flexibility.Peptidoglycan Composition and StructurePeptidoglycan, the core of the bacterial cell wall, comprises alternating units of N-acetylglucosamine (NAG) and...
Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
Production of Antibiotics01:27

Production of Antibiotics

Penicillin, one of the earliest and most widely used antibiotics, is produced industrially by the filamentous fungus Penicillium chrysogenum. Large stirred-tank bioreactors ranging from tens to hundreds of thousands of liters maintain tightly controlled temperature, pH, and dissolved oxygen conditions to support fungal metabolism and maximize antibiotic yield. Penicillin is a secondary metabolite, synthesized primarily during the stationary growth phase, which requires a carefully managed...
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...