A5085062711- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Inorganic Chemistry and Materials
- Bacterial biofilms and quorum sensing
- Click Chemistry and Applications
- Solid-state spectroscopy and crystallography
- Protein Structure and Dynamics
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Advanced biosensing and bioanalysis techniques
- Receptor Mechanisms and Signaling
- Cardiac electrophysiology and arrhythmias
- Cell Image Analysis Techniques
- Synthesis and biological activity
- 3D Printing in Biomedical Research
- Porphyrin Metabolism and Disorders
- Magnetism in coordination complexes
- Cancer therapeutics and mechanisms
- Biochemical and Molecular Research
- Steroid Chemistry and Biochemistry
- Antimicrobial Peptides and Activities
- Glycosylation and Glycoproteins Research
Bicycle Therapeutics (United Kingdom)
2020-2024
MRC Laboratory of Molecular Biology
2016-2023
Medical Research Council
2018
ABSTRACT Bacterial cell division in many organisms involves a constricting cytokinetic ring that is orchestrated by the tubulin-like protein FtsZ. FtsZ forms dynamic filaments close to membrane at site of have recently been shown treadmill around ring, guiding septal wall synthesis. Here, using X-ray crystallography Staphylococcus aureus (SaFtsZ), we reveal how an can adopt two functionally distinct conformations, open and closed. The form found SaFtsZ formed crystals also soluble...
Protein filaments are used in myriads of ways to organize other molecules within cells. Some filament-forming proteins couple the hydrolysis nucleotides their polymerization cycle, thus powering movement molecules. These termed cytomotive. Only members actin and tubulin protein superfamilies known form cytomotive filaments. We examined basis cytomotivity via structural studies cycles homologs from across tree life. analyzed published data performed experiments designed disentangle functional...
Abstract Penicillin binding proteins (PBPs) are well validated antimicrobial targets, but the prevalence of β-lactamase driven resistance and, more rarely, target-based mutations, necessitates new classes PBP-targeting drugs. Here we describe discovery and optimisation novel, bicyclic peptide (Bicycle ® ) inhibitors E. coli PBP3 ( Ec PBP3) using a proprietary phage display platform, their conjugation to linear peptides confer outer membrane permeation. These molecules exhibited high-affinity...
Positioning of the division site in many bacterial species relies on Min CDE system, which prevents cytokinetic Z‐ring from assembling anywhere but mid‐cell, through an oscillatory diffusion‐reaction mechanism. MinD dimers bind to membranes and, via their partner MinC, inhibit polymerization cell protein FtsZ into Z‐ring. MinC and form polymeric assemblies solution membranes. Here, we report high‐resolution cryo‐ EM structure copolymeric filaments Pseudomonas aeruginosa CD . The consist...
Summary Protein filaments are used in myriads of ways to organise other molecules space and time within cells. Some filament-forming proteins couple the hydrolysis nucleotides their polymerisation cycle, thus powering directed movement molecules. These termed cytomotive. Only members actin tubulin protein superfamilies known form cytomotive filaments. We sought examine basis cytomotivity via structural studies cycles homologues from across tree life. analysed published data performed new...
The treatment of infection by Gram-negative bacteria is increasingly challenging as resistance to existing antibiotics spreads. Constrained peptides, selected for high target specificity and affinity via library display technologies, are an emerging therapeutic modality in many disease areas may be a fertile source new antibiotics. Currently, the utility constrained peptides other large molecules limited outer membrane (OM) barrier bacteria. However, addition certain moieties can confer...
Abstract Bactofilins are small beta-helical proteins that form cytoskeletal filaments in a range of bacteria. have diverse functions: Caulobacter crescentus involved cell stalk formation whereas Myxococcus xanthus aid chromosome segregation and motility. The precise molecular architecture bactofilin has remained unclear. Here we revealed by sequence analyses electron microscopy addition to wide distribution across bacteria archaea, bactofilins also present few eukaryotic cells such as...
Abstract Bacterial cell division in many organisms involves a constricting cytokinetic ring that is orchestrated by the tubulin-like protein FtsZ. FtsZ forms dynamic filaments close to membrane at site of have recently been shown treadmill around ring, guiding septal wall synthesis. Here, using X-ray crystallography Staphylococcus aureus SaFtsZ we reveal how an can adopt two functionally distinct conformations, open and closed. The form found formed crystals also soluble E. coli as deduced...
Abstract Positioning of the division site in many bacterial species relies on MinCDE system, which prevents cytokinetic Z-ring from assembling anywhere but mid-cell, through an oscillatory diffusion-reaction mechanism. MinD dimers bind to membranes and, via their partner MinC, inhibit polymerisation cell protein FtsZ into Z-ring. MinC and form polymeric assemblies solution membranes. Here, we report high-resolution cryo-EM structure copolymeric filaments Pseudomonas aeruginosa MinCD. The...