A5064852155- thermodynamics and calorimetric analyses
- Drug Transport and Resistance Mechanisms
- Protist diversity and phylogeny
- Computational Drug Discovery Methods
- Olfactory and Sensory Function Studies
- ATP Synthase and ATPases Research
- HIV/AIDS drug development and treatment
- Mitochondrial Function and Pathology
- Monoclonal and Polyclonal Antibodies Research
- Advanced Chemical Sensor Technologies
- Biochemical Analysis and Sensing Techniques
- Cancer therapeutics and mechanisms
- Chemical Synthesis and Analysis
- Photosynthetic Processes and Mechanisms
- Coenzyme Q10 studies and effects
- Amino Acid Enzymes and Metabolism
- Pharmacological Effects and Toxicity Studies
- Porphyrin and Phthalocyanine Chemistry
- Allelopathy and phytotoxic interactions
- Neonatal Respiratory Health Research
- Pharmacological Effects of Natural Compounds
- Pneumocystis jirovecii pneumonia detection and treatment
- Metal complexes synthesis and properties
- Influenza Virus Research Studies
- Plant Parasitism and Resistance
Heptares Therapeutics (United Kingdom)
2024
MRC Mitochondrial Biology Unit
2012-2020
Medical Research Council
2012-2020
University of Oxford
2018-2020
Wellcome Trust
2013
Abstract Complex I is the first and largest enzyme of respiratory chains in bacteria mitochondria. The mechanism which couples spatially separated transfer electrons to proton translocation complex not known. Here we report five crystal structures T. thermophilus with NADH or quinone-like compounds. We also determined cryo-EM major minor native states complex, differing position peripheral arm. Crystal show that binding compounds (but NADH) leads a related global conformational change,...
A major challenge in drug development is the optimization of intestinal absorption and cellular uptake. successful strategy has been to develop prodrug molecules, which hijack solute carrier (SLC) transporters for active transport into body. The proton-coupled oligopeptide transporters, PepT1 PepT2, have successfully targeted using this approach. Peptide display a remarkable capacity recognize diverse library di- tripeptides, making them extremely promiscuous contributors pharmacokinetic...
The CC chemokine receptor 6 (CCR6) is a potential target for chronic inflammatory diseases. Previously, we reported an active CCR6 structure in complex with its cognate CCL20, revealing the molecular basis of activation. Here, present two inactive structures ternary complexes different allosteric antagonists, CCR6/SQA1/OXM1 and CCR6/SQA1/OXM2. oxomorpholine analogues, OXM1 OXM2 are highly selective antagonists which bind to extracellular pocket disrupt activation network. An energetically...
Mammals produce volatile odours that convey different types of societal information. In Homo sapiens, this is now recognised as body odour, a key chemical component which the sulphurous thioalcohol, 3-methyl-3-sulfanylhexan-1-ol (3M3SH). Volatile 3M3SH produced in underarm result specific microbial activity, act on odourless dipeptide-containing malodour precursor molecule, S-Cys-Gly-3M3SH, secreted axilla (underarm) during colonisation. The mechanism by these bacteria recognise...
Complex I (NADH:ubiquinone oxidoreductase) is central to cellular energy production, being the first and largest enzyme of respiratory chain in mitochondria. It couples electron transfer from NADH ubiquinone with proton translocation across inner mitochondrial membrane involved a wide range human neurodegenerative disorders. Mammalian complex composed 44 different subunits, whereas ‘minimal’ bacterial version contains 14 highly conserved ‘core’ subunits. The L-shaped assembly consists...
Abstract The CC chemokine receptor 6 (CCR6) is a potential target for chronic inflammatory diseases such as psoriasis and bowel disease. Previously, we reported an active CCR6 structure in complex with its cognate CCL20, revealing the molecular basis of activation mediated by CCL20. Here, present two inactive structures determined cryo-EM ternary complexes different allosteric antagonists, CCR6/SQA1/OXM1 CCR6/SQA1/OXM2. OXM1 OXM2 are oxomorpholine (OXM) analogues which highly selective...
Abstract A major challenge in drug development is the optimisation of intestinal absorption and cellular uptake. successful strategy has been to develop prodrug molecules, which hijack solute carrier (SLC) transporters for active transport into body. The proton coupled oligopeptide transporters, PepT1 PepT2, have successfully targeted using this approach. Peptide display a remarkable capacity recognise diverse library di‐ tri-peptides, making them extremely promiscuous contributors...