Related Experiment Video

Updated: Jun 18, 2026

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit
22:10

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit

Published on: June 28, 2013

Crystal structures of penicillin-binding proteins 4 and 5 from Haemophilus influenzae

Fumihiro Kawai1, Thomas B Clarke, David I Roper

  • 1Yokohama City University, Suehiro 1-7-29, Tsurumi, Yokohama 230-0045, Japan.

Journal of Molecular Biology
|December 5, 2009
PubMed

Insights

Researchers determined structures of penicillin-binding proteins (PBPs) from Haemophilus influenzae. Novel beta-lactams show antimicrobial activity, offering insights into PBP inhibition mechanisms.

Area of Science:

  • Microbiology
  • Structural Biology
  • Medicinal Chemistry

Background:

  • Haemophilus influenzae is a common pediatric respiratory pathogen.
  • Penicillin-binding proteins (PBPs) are key targets for beta-lactam antibiotics.
  • Understanding PBP structure-activity relationships is crucial for developing new antimicrobials.

Purpose of the Study:

  • To determine the high-resolution apo crystal structures of PBP4 and PBP5 from H. influenzae.
  • To design novel beta-lactam molecules with antimicrobial activity.
  • To elucidate the structural basis of beta-lactam interaction with PBP4.

Main Methods:

  • X-ray crystallography was used to determine apo and complexed structures.
  • Novel beta-lactam compounds were designed and synthesized.
  • Structural comparison of apo and drug-bound PBP4 was performed.

Main Results:

  • High-resolution apo crystal structures of PBP4 and PBP5 were obtained.
  • Novel beta-lactams exhibited antimicrobial activity.
  • Complex structures revealed that beta-lactams disturb PBP4 structure and diffraction.
  • Structural insights into PBP4's penicillin-sensing mechanism were gained.

Conclusions:

  • The study provides structural insights into beta-lactam inhibition of H. influenzae PBPs.
  • Novel beta-lactams demonstrate potential as antimicrobial agents.
  • Structural differences explain varying susceptibility of PBP4 and PBP5 to beta-lactams.

More Related Videos

Biochemical and Structural Characterization of the Carbohydrate Transport Substrate-binding-protein SP009208:53

Biochemical and Structural Characterization of the Carbohydrate Transport Substrate-binding-protein SP0092

Published on: October 2, 2017

Production, Crystallization and Structure Determination of C. difficile PPEP-1 via Microseeding and Zinc-SAD13:34

Production, Crystallization and Structure Determination of C. difficile PPEP-1 via Microseeding and Zinc-SAD

Published on: December 30, 2016

Related Concept Videos

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...
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...
Peptidoglycan Synthesis01:28

Peptidoglycan Synthesis

Structure of PeptidoglycanPeptidoglycan is a vital structural component of the bacterial cell wall, providing mechanical strength and shape to the cell. It consists of repeating units of two sugars—N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)—linked by β-1,4 glycosidic bonds. These sugar chains are cross-linked by short peptide chains, forming a mesh-like polymer that surrounds the bacterial plasma membrane.Cytoplasmic Phase – Precursor SynthesisPeptidoglycan biosynthesis begins in...
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...
Gene Families01:57

Gene Families

Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Cytoskeletal Proteins in Bacteria01:29

Cytoskeletal Proteins in Bacteria

Bacterial cells were initially considered simple, randomly organized structures lacking a cytoskeleton. However, the discovery of cytoskeleton homologs in bacteria led to the change of this opinion. Bacterial cytoskeletal filaments regulate the cell shape, cell polarity, cell division, and partitioning of plasmids during cell division. It was later discovered that bacterial cytoskeletal proteins, mainly actin and tubulin homologs, are diverse compared to their eukaryotic counterparts. On the...