A5015913368- Photosynthetic Processes and Mechanisms
- Photoreceptor and optogenetics research
- Spectroscopy and Quantum Chemical Studies
- Bacterial Genetics and Biotechnology
- Neuropeptides and Animal Physiology
- Blood Coagulation and Thrombosis Mechanisms
- RNA and protein synthesis mechanisms
- HIV/AIDS drug development and treatment
- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- Hemoglobin structure and function
- Electrochemical Analysis and Applications
- Protein Structure and Dynamics
- Light effects on plants
- Hepatitis C virus research
- Antibiotic Resistance in Bacteria
- Metabolism, Diabetes, and Cancer
- Protein Kinase Regulation and GTPase Signaling
- Radiopharmaceutical Chemistry and Applications
- Enzyme Structure and Function
- Lanthanide and Transition Metal Complexes
- Electrochemical sensors and biosensors
- Atrial Fibrillation Management and Outcomes
Newcastle University
2023-2024
GlaxoSmithKline (United Kingdom)
2001-2020
The Francis Crick Institute
2017-2018
University of Cambridge
2001
Molecular Discovery (United Kingdom)
1998
University of Oxford
1998
Columbia University
1993
Southwestern Medical Center
1993
UCB Pharma (United Kingdom)
1991-1993
The University of Texas Southwestern Medical Center
1993
AMP-activated protein kinase (AMPK) plays a major role in regulating metabolism and has attracted significant attention as therapeutic target for treating metabolic disorders. AMPK activity is stimulated more than 100-fold by phosphorylation of threonine 172 (Thr172). Binding AMP to the γ subunit allosterically activates kinase. Additionally, many small molecules, e.g. 991, have been identified that bind between domain carbohydrate-binding module β subunit, stabilising their interaction...
A 130-residue fragment (D1-D4) taken from a fibronectin-binding protein of Staphylococcus aureus, which contains four repeats and is unfolded but biologically active at neutral pH, has been studied extensively by NMR spectroscopy. Using heteronuclear multidimensional techniques, the conformational properties D1-D4 have defined both global local level. Diffusion studies give an average effective radius 26.2 +/- 0.1 A, approximately 75% larger than that expected for globular this size....
Two-component signal transduction (TCST) pathways are regulatory systems that highly homologous throughout the bacterial kingdom. Their established role in virulence and absence vertebrates has made TCST an attractive target for therapeutic intervention. However, such have yet to yield success development of novel antibiotics. CheY serves as a prototype analysis response regulator function. The protein structure exhibits several conformations by both X-ray nuclear magnetic resonance (NMR)...
Thermostabilization by mutagenesis is one method which has facilitated the determination of high-resolution structures adenosine A2A receptor (A(2A)R). Sets mutations were identified, both thermostabilized and resulted in preferential agonist (Rag23 mutant) or antagonist (Rant5 Rant21) binding forms as assessed radioligand analysis. While ligand-binding profiles these mutants are known, effects have on activation downstream signalling less well characterized.Here we investigated...
Near-u.v. and far-u.v. c.d. spectra of human alpha-calcitonin-gene-related peptide (h alpha CGRP), analogues fragments CGRP amylin were recorded in aqueous solution trifluoroethanol (TFE)/water mixtures. All peptides contained significant amounts alpha-helix solution, this amount increased on adding TFE. The helical content was unaffected by pH salt. However, much less helix than the spectrum more temperature-sensitive. A band near-u.v. (but not present amylin) attributed to disulphide bond...
A widely accepted model for the structure of facilitative glucose transporters (GLUTs) predicts that they form 12 transmembrane alpha-helices and highly conserved sequence Ile-386-Ala-405 in GLUT1 is intracellular. We raised a polyclonal antibody against synthetic peptide encompassing this found treatment increased 2-deoxy-D-glucose (DOG) uptake Xe-nopus oocytes expressing GLUT1, GLUT2, or GLUT4 only when applied to extracellular side. This effect was dose dependent specifically blocked by...
Photosystem I particles were washed twice in either 0, 50 or 100% water‐saturated diethyl ether. It was found that the characteristic electron spin resonance signal associated with acceptor A 1 progressively lost increasing percentage saturation of Light‐induced flow to terminal iron‐sulphur acceptors inhibited although these still present and could be chemically reduced. The kinetics optical measurements P700 + re‐reduction at 820 nm following ether washing consistent removal .
We have characterized the induction kinetics of approximately 1,700 proteins during entry into and survival in carbon-starved stationary phase by Mycobacterium smegmatis. Strikingly, among patterns expression observed were a group that expressed exponential-phase cultures severely repressed 48-h stationary-phase (Spr or stationary-phase-repressed proteins) but synthesized again at high levels > =128-day (Spr(128) proteins). A number Spr(128) identified, they included heat shock protein DnaK,...
alpha-Calcitonin-gene-related peptide (alpha CGRP) lacking its C-terminal phenylalaninamide residue was found not to bind receptor as did full-length (amidated) alpha CGRP. Investigation of the structure these peptides by c.d. and n.m.r. revealed no significant difference, so it seemed that effect deleting on biological activity CGRP disruption peptide's structure. Thus is an important factor in this ligand-receptor interaction, group itself may interact directly with receptor.
Abstract Genome duplication is essential for the proliferation of cellular life and this process generally initiated by dedicated replication proteins at chromosome origins. In bacteria, DNA ubiquitous DnaA protein, which assembles into an oligomeric complex origin ( oriC ) that engages both double-stranded (dsDNA) single-stranded (ssDNA) to promote duplex opening. However, mechanism specifically opening a was unknown. Here we show Bacillus subtilis ATP continuous oligomer site melting,...
SummaryNuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy have been used to characterize the conformation of putative cytoplasmic domain phospholamban (PLB), an oligomeric membrane-bound protein which regulates activity cardiac sarcoplasmic reticulum Ca2 +-dependent ATPase. In aqueous solution 25-residue peptide adopts a number rapidly interconverting conformers with no secondary structural type obviously predominating. However, in trifluoroethanol (TFE) conformation,...
EPR signals due to c ‐type cytochromes in Rhodopseudomonas viridis reaction centres are reported. Haems with E m = 380 mV (1), 310 (1) and about 0 (2) were identified. At redox potentials where the low‐potential oxidised, but high‐potential reduced, photooxidation of is observed as Q A photoreduced by low‐temperature (15 K) illumination. Cyt ‐556→cyt ‐559→reaction centre→Q However, signal attributed only 30–40% intensity narrower than that when all haems reduced. It suggested reduction...
The absorbance maximum (630 nm) of reduced cytochrome d in Escherichia coli membrane particles was diminished by 160 μM AgNO 3 or NaNO and accompanied the formation a species with an absorption at 640–645 nm. Nitrite, trioxodinitrate nitric oxide elicited qualitatively similar, but faster, changes spectrum , suggesting that nitrosyl complex may be involved all cases. In direct contrast to earlier report, silver ions (160 υM) were without effect on α‐bands cytochromes d, b 1 .