A5003106898- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Biochemical and Molecular Research
- Enzyme Structure and Function
- Trypanosoma species research and implications
- Crystallography and molecular interactions
- Chemical Synthesis and Analysis
- Magnetism in coordination complexes
- Vitamin K Research Studies
- Nicotinic Acetylcholine Receptors Study
- Porphyrin and Phthalocyanine Chemistry
- Carbohydrate Chemistry and Synthesis
- Research on Leishmaniasis Studies
- Plant biochemistry and biosynthesis
- Organometallic Complex Synthesis and Catalysis
- Calcium signaling and nucleotide metabolism
- Biochemical Acid Research Studies
- Metal complexes synthesis and properties
- Toxin Mechanisms and Immunotoxins
- Crystal structures of chemical compounds
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Pneumocystis jirovecii pneumonia detection and treatment
- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
Western University
2023-2024
University of Dundee
2010-2024
Wellcome Centre for Anti-Infectives Research
2022-2024
Heidelberg Institute for Theoretical Studies
2017
Wellcome Trust
2017
University of Edinburgh
2002-2012
University of Arizona
2004-2010
Philipps University of Marburg
2009
Newcastle University
2008
University of California, Santa Cruz
2008
We report structure−activity relationships for organometallic RuII complexes of the type [(η6-arene)Ru(XY)Cl]Z, where XY is an N,N- (diamine), N,O- (e.g., amino acidate), or O,O- β-diketonate) chelating ligand, arene ranges from benzene derivatives to fused polycyclic hydrocarbons, and Z usually PF6. The X-ray structures 13 are reported. All have characteristic “piano-stool” geometry. most active toward A2780 human ovarian cancer cells contained = ethylenediamine (en) extended arenes....
The synthesis and X-ray structure (as the tetrahydrate) of platinum(IV) complex trans,trans,trans-[Pt(N(3))(2)(OH)(2)(NH(3))(2)] 3 are described its photochemistry photobiology compared with those cis isomer cis,trans,cis-[Pt(N(3))(2)(OH)(2)(NH(3))(2)] 4. Complexes 4 potential precursors anticancer drug cisplatin inactive trans transplatin, respectively. is octahedral, contains almost linear azide ligands, adopts a layer extensive intermolecular hydrogen bonding. intense...
TarO (http://www.compbio.dundee.ac.uk/taro) offers a single point of reference for key bioinformatics analyses relevant to selecting proteins or domains study by structural biology techniques. The protein sequence is analysed 17 algorithms and compared 8 databases. gathers putative homologues, including orthologues, then obtains predictions properties these sequences crystallisation propensity, disorder post-translational modifications. Analyses are run on high-performance computing cluster,...
Cryptosporidiosis is a diarrheal disease caused by infection with Cryptosporidium spp. parasites and leading cause of death in malnourished children worldwide. The only approved treatment, nitazoxanide, has limited efficacy this at-risk patient population. Additional safe therapeutics are urgently required to tackle unmet medical need. However, the development anti-cryptosporidial drugs hindered lack understanding optimal compound properties treat gastrointestinal infection. To address...
The external layer of the Gram-negative bacterial outer membrane is primarily composed a protective, selectively permeable LPS. biosynthesis LPS relies on UDP-3-O-acyl-glucosamine N-acyltransferase (LpxD), which transfers 3-hydroxy-arachidic acid from acyl carrier protein to 2' amine UDP-3-O-myristoyl glucosamine in Chlamydia trachomatis. Our crystallographic study reveals that LpxD homotrimer, each subunit constructed novel combination an N-terminal uridine-binding domain, core...
2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase (IspF) catalyzes the conversion of 4-diphosphocytidyl-2C-methyl-D-erythritol-2-phosphate to and cytidine monophosphate in production isoprenoid-precursors via methylerythritol phosphate biosynthetic pathway. IspF is found protozoan Plasmodium falciparum, a parasite that causes cerebral malaria, as well many Gram-negative bacteria such Burkholderia cenocepacia. represents potential target for development broad-spectrum antimicrobial drugs...
There is a pressing need for new medicines to prevent and treat malaria. Most antimalarial drug discovery reliant upon phenotypic screening. However, with the development of improved target validation strategies, target-focused approaches are now being utilized. Here, we describe toolkit support therapeutic exploitation promising target, lysyl tRNA synthetase (PfKRS). The includes resistant mutants probe resistance mechanisms on-target engagement specific chemotypes; hybrid KRS protein...
Abstract Tuberculosis is a major global cause of both mortality and financial burden mainly in low middle-income countries. Given the significant ongoing rise drug-resistant strains Mycobacterium tuberculosis within clinical setting, there an urgent need for development new, safe effective treatments. Here drug-like series based on fused dihydropyrrolidino-pyrimidine scaffold described. The has been developed against M. lysyl-tRNA synthetase (LysRS) cellular studies support this mechanism...
The platinum diimine dithiolate complex, [Pt(2,2′-bipyridyl-5,5′-dicarboxylicacid)(3,4-toluenedithiolate)] ([Pt(5,5′-dcbpy)(tdt)]) and its tetrabutylammonium salt [TBA]2[Pt(5,5′-dcbpy)(tdt)] have been prepared, spectroscopically electrochemically characterised attached on to TiO2 substrate be used as solar cell sensitisers. A single-crystal X-ray structure was obtained for [TBA]2[Pt(5,5′-dcbpy)(tdt)]·EtOH·EtOAc. effect of the position two carboxylic acid substituents electrochemistry...
Summary The protozoan Trypanosoma brucei has a functional pteridine reductase ( Tb PTR1), an NADPH‐dependent short‐chain that participates in the salvage of pterins, which are essential for parasite growth. PTR1 displays broad‐spectrum activity with pterins and folates, provides metabolic bypass inhibition trypanosomatid dihydrofolate therefore compromises use antifolates treatment trypanosomiasis. Catalytic properties recombinant by archetypal antifolate methotrexate have been characterized...
Two crystalline phases of aniline have been investigated by a combination single crystal X-ray diffraction data on aniline-h7 and neutron powder aniline-d7. Phase-I, which is formed cooling the liquid at ambient pressure, monoclinic (P21/c). Orthorhombic (Pna21) phase-II was crystallised 0.84 GPa room temperature structurally characterised pressures up to 7.3 GPa. The strongest intermolecular interactions in both structures are NH⋯π contacts NH⋯N H-bonds. These occur within layers phases,...
Recrystallisation of paracetamol from a solution in methanol at pressure 0.62 GPa gives new 1:1 solvate that has been characterised by single crystal X-ray diffraction.
The synthesis and materials properties of a new liquid crystalline phthalocyanine, octakis (2-benzyloxyethylsulfanyl) copper (II) 2, are reported. This phthalocyanine possesses eight benzyl-terminated side chains with thioether links to the Pc core, which promote greater interaction between discotic mesogens than has been seen in previous Pcs reported from this group had alkoxy-based chains. use these promotes red-shift Q-band absorbance spectrum, small decreases first oxidation potential,...
The tripodal ligands hydrotris(N-ethyl-2-mercaptoimidazol-1-yl)borate (NaTmEt) (1) and hydrotris(N-benzyl-2-mercaptoimidazol-1-yl)borate (NaTmBn) (2), analogues of the hydrotris(N-methyl-2-mercaptoimidazol-1-yl)borate ligand (Tm) containing alternative nitrogen substituents, have been employed to examine racemization their C3-symmetric complexes with both four- six-coordinate metals. react at room temperature metal halides provide complexes. syntheses four-coordinate [TmEtZnCl] (3),...
The first committed step in the classical biosynthetic route to menaquinone (vitamin K(2)) is a Stetter-like conjugate addition of alpha-ketoglutarate with isochorismate. This reaction catalyzed by thiamine diphosphate and metal-ion-dependent 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate synthase (MenD). medium-resolution (2.35 A) crystal structure Bacillus subtilis MenD cofactor Mn(2+) has been determined. Based on structure-sequence comparisons modeling, two-stage...
The preparation, EPR spectra, and crystal structures of octaethyltetraphenylporphyrinatoiron(III) having two imidazole, N-benzylimidazole, N-methylimidazole axial ligands are reported, [(OETPP)Fe(HIm)2]Cl, [(OETPP)Fe(N-BzIm)2]Cl, [(OETPP)Fe(N-MeIm)2]Cl. Despite large variation in ligand size, the unit cell parameters for all complexes very similar; each structure has same basic motif, with voids formed by extended porphyrin framework (filled ordered or disordered solvent), which allows...
Gas-phase photoelectron spectroscopy and density functional theory have been used to investigate the electronic structures of open-shell bent vanadocene compounds with chelating dithiolate ligands, which are minimum molecular models active sites pyranopterin Mo/W enzymes. The Cp2V(dithiolate) [where is 1,2-ethenedithiolate (S2C2H2) or 1,2-benzenedithiolate (bdt), Cp cyclopentadienyl] provide access a 17-electron, d1 electron configuration at metal center. Comparison previously studied...
The twin-arginine translocation (Tat) pathway is a protein targeting system found in bacteria, archaea, and chloroplasts. Proteins are directed to the Tat translocase by N-terminal signal peptides containing SRRxFLK "twin-arginine" amino acid motifs. key feature of its ability transport fully folded proteins across ionically sealed membranes. For this reason has evolved for assembly extracytoplasmic redox enzymes that must bind cofactors, so fold, prior export. It important only...
Pteridine reductase-1 (PTR1) is a promising drug target for the treatment of trypanosomiasis. We investigated potential previously identified class thiadiazole inhibitors Leishmania major PTR1 activity against Trypanosoma brucei (Tb). solved crystal structures several TbPTR1-inhibitor complexes to guide structure-based design new derivatives. Subsequent synthesis and enzyme- cell-based assays confirm new, mid-micromolar TbPTR1 with low toxicity. In particular, compound 4m,...
Pteridine reductase (PTR1) is a potential target for drug development against parasitic Trypanosoma and Leishmania species. These protozoa cause serious diseases which current therapies are inadequate. High-resolution structures have been determined, using data between 1.6 1.1 Å resolution, of T. brucei PTR1 in complex with pemetrexed, trimetrexate, cyromazine 2,4-diaminopyrimidine derivative. The provide insight into the interactions formed by new molecular entities enzyme active site...
The nonmevalonate route to isoprenoid biosynthesis is essential in Gram-negative bacteria and apicomplexan parasites. enzymes of this pathway are absent from mammals, contributing their appeal as chemotherapeutic targets. One enzyme, 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase (IspF), has been validated a target by genetic approaches bacteria. Virtual screening against Escherichia coli IspF (EcIspF) was performed combining hierarchical filtering methodology with molecular docking....