A5026488732- Drug Transport and Resistance Mechanisms
- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Protein Structure and Dynamics
- Prion Diseases and Protein Misfolding
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Trace Elements in Health
- Pancreatic function and diabetes
- Nerve injury and regeneration
- Antibiotics Pharmacokinetics and Efficacy
- Metabolism, Diabetes, and Cancer
- Antifungal resistance and susceptibility
- Protein Interaction Studies and Fluorescence Analysis
- Neurological diseases and metabolism
- Fungal Infections and Studies
- Neurogenesis and neuroplasticity mechanisms
- Erythrocyte Function and Pathophysiology
- Signaling Pathways in Disease
- Microfluidic and Capillary Electrophoresis Applications
- Glycosylation and Glycoproteins Research
- Pediatric Hepatobiliary Diseases and Treatments
- Fungal and yeast genetics research
- Cancer therapeutics and mechanisms
- ATP Synthase and ATPases Research
Durham University
2008-2021
Glenmark Pharmaceuticals (Switzerland)
2015
Novartis Institutes for BioMedical Research
2004-2012
Novartis (Switzerland)
2003-2012
University of Leeds
1994-2008
University of Chicago
2005
Argonne National Laboratory
2005
University of Toronto
2005
University of Glasgow
1998-2002
Wayne State University
1999-2002
Environmental arsenic is a world-wide health issue, making it imperative for us to understand mechanisms of metalloid uptake and detoxification. The predominant intracellular form the highly mephitic arsenite, which detoxified by removal from cytosol. What prevents arsenite toxicity as diffuses through cytosol efflux systems? Although copper regulated metallochaperones, no chaperones involved in conferring resistance other metals have been identified. In this article, we report...
Here we identify an 11-residue helical module in the unique N-terminal region of cyclic AMP-specific phosphodiesterase PDE4A1 that determines association with phospholipid bilayers and shows a profound selectivity for interaction phosphatidic acid (PA). This contains core bilayer insertion unit is formed by two tryptophan residues, Trp(19) Trp(20), whose orientation optimized Leu(16):Val(17) pairing. Ca(2+), at submicromolar levels, interacts Asp(21) this serves to gate insertion, which...
ABSTRACT Xanthomonas oryzae pv. oryzicola, the cause of bacterial leaf streak in rice, possesses clusters hrp genes that determine its ability to elicit a hypersensitive response (HR) nonhost tobacco and pathogenicity host rice. A 27-kb region genome X. oryzicola (RS105) was identified sequenced, revealing 10 , 9 hrc ( conserved), 8 hpa -associated) 7 regulatory plant-inducible promoter boxes. While from hpa2 hpaB hrpF operon resembled corresponding other xanthomonads, - incorporated an...
Multidrug resistance in Gram-negative bacteria arises part from the activities of tripartite drug efflux pumps. In pathogen Vibrio cholerae, one such pump comprises inner membrane proton antiporter VceB, periplasmic adaptor VceA, and outer channel VceC. Here, we report crystal structure VceC at 1.8 A resolution. The trimeric is organized lattice within laminar arrays that resemble membranes. well resolved detergent molecule this array interacts with transmembrane beta-barrel domain a fashion...
Gram-negative bacteria utilize specialized machinery to translocate drugs and protein toxins across the inner outer membranes, consisting of a tripartite complex composed an membrane secondary or primary active transporter (IMP), periplasmic fusion protein, channel. We have investigated assembly function MacAB/TolC system that confers resistance macrolides in Escherichia coli. The MacA not only stabilizes by interacting with both MacB TolC, but also has role regulating MacB, apparently...
The correct folding and assembly of proteins within the endoplasmic reticulum (ER) are prerequisites for subsequent transport from this organelle to Golgi apparatus. mechanisms underlying ability cell recognize retain unassembled or malfolded generally require binding molecular chaperones ER. One classic example process occurs during biosynthesis procollagen. Here partially folded intermediates retained prevented secretion, leading a build up unfolded chains cell. accumulation these vitamin...
The association of the prion protein (PrP) with sphingolipid- and cholesterol-rich lipid rafts is instrumental in pathogenesis neurodegenerative diseases. Although glycosylphosphatidylinositol (GPI) anchor an exoplasmic determinant raft association, PrP remained raft-associated human neuronal cells even when GPI was deleted or substituted for a transmembrane indicating that ectodomain contains localization signal. transmembrane-anchored occurred independently Cu(II) binding as it failed to...
Nogo-66 receptor (NgR) has recently been identified as the neuronal of myelin-associated proteins Nogo-A, oligodendrocyte protein (OMgp) and glycoprotein (MAG), mediates inhibition axonal regeneration both in vitro vivo. Through database searches, we have two novel (NgRH1 NgRH2) that turned out to be homologous their primary structures, biochemical properties expression patterns NgR. Like NgR, homologues contain eight leucine-rich repeats (LRR) flanked by a repeat C-terminus (LRRCT)...
The substrate specificity of the major cysteinyl proteinase parasitic protozoan Trypanosoma cruzi (cruzipain) was investigated, by combinatorial replacement amino acid residues at positions P5-P'5, using a fluorescent quenched solid-phase library assay. Positively charged appear to be general preference in P5-P3 and P'5-P'3 positions, while hydrophobic residue always required P2 position. A broad range acids could accepted P'1 clear difference terms between cruzipain human cathepsin L...
The multiple transferable resistance (mTR) pump from Neisseria gonorrhoeae MtrCDE multidrug is assembled the inner and outer membrane proteins MtrD MtrE periplasmic fusion protein MtrC. Previously we established that while there a weak interaction of MtrE, MtrC binds with relatively high affinity to both MtrE. conferred antibiotic only when it was expressed MtrC, suggesting these form functional tripartite complex in which bridges Furthermore, demonstrated interacts an intraprotomer groove...
We have isolated and characterized cDNA genomic clones that encode a 70 kDa heat shock protein (Hsp70) from the dimorphic human pathogenic fungus Paracoccidioides brasiliensis . The gene encodes 649‐amino‐acid showing high identity with other members of hsp70 family. is induced during both yeast cells at 42°C mycelial to transition. A differential expression this can be observed between forms, much higher level in yeast. found two introns 178 72 nucleotides P. gene. Splicing these regulated...