- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- Hemoglobin structure and function
- Biochemical and Molecular Research
- Glycosylation and Glycoproteins Research
- Protein Structure and Dynamics
- Genomics and Phylogenetic Studies
- Phytase and its Applications
- Carbohydrate Chemistry and Synthesis
- Microbial Metabolic Engineering and Bioproduction
- Photosynthetic Processes and Mechanisms
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- Porphyrin Metabolism and Disorders
- Microbial Community Ecology and Physiology
- Microbial metabolism and enzyme function
- Advanced biosensing and bioanalysis techniques
- Cellular transport and secretion
- Crystallization and Solubility Studies
- Sphingolipid Metabolism and Signaling
- X-ray Diffraction in Crystallography
- CRISPR and Genetic Engineering
The University of Texas at Austin
2011-2025
UiT The Arctic University of Norway
2010-2015
AstraZeneca (United Kingdom)
2014
University of St Andrews
2006-2011
Ewha Womans University
2010
Osaka University
2010
Yonsei University
2010
Istituto Pasteur
2003-2009
Sapienza University of Rome
2008-2009
University of Edinburgh
2009
Nitric oxide (NO) has been implicated as mediator in a variety of physiological functions, including neurotransmission, platelet aggregation, macrophage function, and vasodilation. The consumption NO by extracellular hemoglobin subsequent vasoconstriction have suggested to be the cause mild hypertensive events reported during vivo trials hemoglobin-based O2 carriers. depletion from endothelial cells is most likely due oxidative reaction with oxyhemoglobin arterioles surrounding tissue. In...
Abstract Type II CRISPR endonucleases are widely used programmable genome editing tools. Recently, CRISPR-Cas systems with highly compact nucleases have been discovered, including Cas9d (a type II-D nuclease). Here, we report the cryo-EM structures of a nuclease (747 amino acids in length) multiple functional states, revealing stepwise process DNA targeting involving conformational switch REC2 domain insertion. Our provide insights into intricately folded guide RNA which acts as structural...
Polygalacturonase-inhibiting proteins (PGIPs) are plant cell wall that protect plants from fungal invasion. They interact with endo polygalacturonases secreted by phytopathogenic fungi, inhibit their enzymatic activity, and favor the accumulation of oligogalacturonides, which activate defense responses. PGIPs members leucine-rich repeat (LRR) protein family in play crucial roles development, against pathogens, recognition beneficial microbes. Here we report crystal structure at 1.7-Å...
The Scottish Structural Proteomics Facility was funded to develop a laboratory scale approach high throughput structure determination. effort successful in that over 40 structures were determined. These and the methods harnessed obtain them are reported here. This report reflects on value of automation but also continued requirement for degree scientific technical expertise. efficiency process poses challenges current paradigm structural analysis publication. In 5 year period we published...
The ardA gene, found in many prokaryotes including important pathogenic species, allows associated mobile genetic elements to evade the ubiquitous Type I DNA restriction systems and thereby assist spread of resistance genes bacterial populations. As such, contributes a major healthcare problem. We have solved structure ArdA protein from conjugative transposon Tn 916 find that it has novel extremely elongated curved cylindrical with defined helical grooves. high density aspartate glutamate...
Hel308 is a superfamily 2 helicase conserved in eukaryotes and archaea. It thought to function the early stages of recombination following replication fork arrest has specificity for removal lagging strand model forks. A homologous constitutes N-terminal domain human DNA polymerase Q. The Drosophila homologue mus301 implicated double break repair meiotic recombination. We have solved high resolution crystal structure from crenarchaeon Sulfolobus solfataricus, revealing five-domain with...
PCNA is a ring-shaped protein that encircles DNA, providing platform for the association of wide variety DNA-processing enzymes utilize sliding clamp to maintain proximity their DNA substrates. homotrimer in eukaryotes, but heterotrimer crenarchaea such as Sulfolobus solfataricus. The three proteins are SsoPCNA1 (249 residues), SsoPCNA2 (245 residues) and SsoPCNA3 (259 residues). heterotrimeric crystallizes space group P21, with unit-cell parameters = 44.8, b 78.8, c 125.6 Å, β 100.5°....
Abstract Our aim is to shed light on the conservation of potential ligand docking sites that play an important role in dynamics globins by using technique filling internal cavities naturally present hemoglobin and myoglobin with xenon atoms. In particular, we high resolution structures Xe‐adduct deoxygenated wild type human a quadruple mutant (L(B10)Y H(E7)Q α β chains). For sake comparison also determined under same experimental conditions complex sperm whale myoglobin. The analysis...
Sphingolipid biosynthesis begins with the condensation of L-serine and palmitoyl-CoA catalyzed by PLP-dependent enzyme serine palmitoyltransferase (SPT). Mutations in human SPT cause hereditary sensory autonomic neuropathy type 1, a disease characterized loss feeling extremities severe pain. The is membrane-bound hetereodimer, most common mutations are located enzymatically incompetent monomer, suggesting "dominant" or regulatory effect. molecular basis how these perturb activity subtle not...
Cathepsin L mutants with the ability to condense silica from solution have been generated and a 1.5 Å crystal structure of one these chimeras allows us rationalise catalytic mechanism silicic acid condensation.
Cycloserine (CS, 4-amino-3-isoxazolidone) is a cyclic amino acid mimic that known to inhibit many essential pyridoxal 5′-phosphate (PLP)-dependent enzymes. Two CS enantiomers are known; D-cycloserine (DCS, also as Seromycin) natural product used treat resistant Mycobacterium tuberculosis infections well neurological disorders since it potent NMDA receptor agonist, and L-cycloserine (LCS) synthetic enantiomer whose usefulness drug has been hampered by its inherent toxicity arising through...
Abstract Serine palmitoyltransferase (SPT) catalyses the first step in de novo biosynthesis of sphingolipids (SLs). It uses a decarboxylative Claisen‐like condensation reaction to couple L ‐serine with palmitoyl‐CoA generate long‐chain base product, 3‐ketodihydrosphingosine. SLs are produced by mammals, plants, yeast, and some bacteria, we have exploited complete genome sequence Sphingomonas wittichii begin analysis bacterial sphingolipid biosynthesis. Here, describe enzymatic...
Schistomiasis is a debilitating parasitic disease which affects 200 million people, causing life-threatening complications in 10% of the patients. This paper reports crystal structure Schistosoma haematobium 28 kDa glutathione S-transferase, multifunctional enzyme involved host-parasite interactions and presently considered as promising vaccine candidate against schistosomiasis. The structures GSH-free enzyme, well partially (approximately 40%) almost fully 80%) GSH-saturated exhibit unique...
Inositol monophosphatase (EC 3.1.3.25) in hyperthermophilic archaea is thought to play a role the biosynthesis of di-myo-inositol-1,1'-phosphate (DIP), an osmolyte unique hyperthermophiles. The Methanococcus jannaschii MJ109 gene product, sequence which substantially homologous that human inositol monophosphatase, exhibits activity but with substrate specificity broader than those bacterial and eukaryotic monophosphatases (it can also act as fructose bisphosphatase). To understand its well...