A5025745736- Pneumonia and Respiratory Infections
- Metal-Catalyzed Oxygenation Mechanisms
- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- Photosynthetic Processes and Mechanisms
- Carbohydrate Chemistry and Synthesis
- Streptococcal Infections and Treatments
- Metalloenzymes and iron-sulfur proteins
- Porphyrin Metabolism and Disorders
- Bacterial Infections and Vaccines
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Antimicrobial Resistance in Staphylococcus
- Metabolism, Diabetes, and Cancer
- Lipid Membrane Structure and Behavior
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Protein Structure and Dynamics
- RNA Research and Splicing
- Analytical Chemistry and Chromatography
- Hemoglobin structure and function
- Helicobacter pylori-related gastroenterology studies
- Cancer, Hypoxia, and Metabolism
Evotec (United Kingdom)
2024
Imperial College London
2015-2023
Charles River Laboratories (United Kingdom)
2021
Instituto de Química Física Blas Cabrera
2004-2015
Medical Research Council
2014
MRC Laboratory of Molecular Biology
2014
Consejo Superior de Investigaciones Científicas
2005-2013
Spanish National Cancer Research Centre
2010
Universidad de Zaragoza
2005
National University of Rosario
2005
VARP is a Rab32/38 effector that also binds to the endosomal/lysosomal R-SNARE VAMP7. binding regulates VAMP7 participation in SNARE complex formation and can therefore influence VAMP7-mediated membrane fusion events. Mutant versions of cannot bind Rab32:GTP, designed on basis ankyrin repeat/Rab32:GTP structure described here, unexpectedly retain endosomal localization, showing recruitment not dependent Rab32 binding. We show mediated by its direct interaction with VPS29, subunit retromer...
Abstract The promising drug target N -myristoyltransferase (NMT) catalyses an essential protein modification thought to occur exclusively at N-terminal glycines (Gly). Here, we present high-resolution human NMT1 structures co-crystallised with reactive cognate lipid and peptide substrates, revealing snapshots of the entire catalytic mechanism from initial final reaction states. Structural comparisons, together biochemical analysis, provide unforeseen details about how reaches a catalytically...
The identification of VHL-binding proteolysis targeting chimeras (PROTACs) that potently degrade the BRM protein (also known as SMARCA2) in SW1573 cell-based experiments is described. These molecules exhibit between 10- and 100-fold degradation selectivity for over closely related paralog BRG1 (SMARCA4). They also selectively impair proliferation H1944 "BRG1-mutant" NSCLC cell line, which lacks functional thus highly dependent on growth, relative to wild-type Calu6 line. In vivo performed...
Scientific Report13 June 2015Open Access Structural insight into the TRIAP1/PRELI-like domain family of mitochondrial phospholipid transfer complexes Xeni Miliara Department Life Sciences, Imperial College London, UK Search for more papers by this author James A Garnett School Biological and Chemical Joseph Priestley Building, Queen Mary, University Takashi Tatsuta Institute Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center...
Pneumococcal bacteriophage-encoded lysins are modular proteins that have been shown to act as enzymatic antimicrobial agents (enzybiotics) in treatment of streptococcal infections. The first x-ray crystal structures the Cpl-1 lysin, encoded by pneumococcal phage Cp-1, complex with three bacterial cell wall peptidoglycan (PG) analogues reported herein. structure is folded two well defined modules, one responsible for anchoring and other, a catalytic module, hydrolyzes PG. Conformational...
Mycobacteria embrace a broad pool of microorganisms causing infections with renowned impact in human health altogether millions deaths every year. From tuberculosis and lepra, caused by Mycobacterium leprae respectively, to emergent/opportunistic pathogens such as abscessus. The battle confront this burden is further challenged limitations the treatments currently available emergence antimicrobial resistance, thus making necessary search for new therapeutic strategies fight these infections....
Phytopathogenic bacteria secrete diverse virulence factors to manipulate host defenses and establish infection. Characterization of the type III secretion system (T3SS)- HrpL-independent secretome (T3-IS) in Pseudomonas savastanoi pv. (Psv), causal agent olive knot disease, identified five secreted LysM-containing proteins (LysM1–LysM5) associated with distinct physiological processes critical for Functional predictions from network analyses suggest that LysM1, LysM2, LysM4 may participate...
Helicobacter pylori establishes life-long infections in the gastric mucosa of over 1 billion people worldwide. In many cases, without specific antimicrobial intervention, H. infected individuals will develop type B gastritis, chronic peptic ulcers and, more rarely, neoplasias. Conventional therapy has been complicated by dramatic increases resistance to macrolides, metronidazole and fluoroquinolones. Here, we report development novel therapeutics that specifically target unique flavodoxin...
Protein-protein interactions (PPIs) are essential and pervasive regulatory elements in biology. Despite the development of a range techniques to probe PPIs living systems, there is dearth approaches capture driven by specific post-translational modifications (PTMs). Myristoylation lipid PTM added more than 200 human proteins, where it may regulate membrane localization, stability or activity. Here we report design synthesis panel novel photocrosslinkable clickable myristic acid analog...
Ferredoxin−NADP+ reductase (FNR) catalyzes the reduction of NADP+ to NADPH in an overall reversible reaction, showing some differences mechanisms between cyanobacterial and higher plant FNRs. During hydride transfer it is proposed that FNR C-terminal Tyr displaced by nicotinamide. Thus, this might be involved not only modulating flavin redox properties, as already shown, but also nicotinamide binding transfer. variants from cyanobacterium Anabaena which has been replaced Trp, Phe, or Ser...
The photosynthetic bacterium Rhodobacter capsulatus contains a ferredoxin (flavodoxin)-NADP(H) oxidoreductase (FPR) that catalyzes electron transfer between NADP(H) and or flavodoxin. structure of the enzyme, determined by X-ray crystallography, two domains harboring FAD binding sites, as is typical FPR structural family. molecule in hairpin conformation which stacking interactions can be established dimethylisoalloxazine adenine moieties. midpoint redox potentials various transitions...
Abstract Flavodoxins, noncovalent complexes between apoflavodoxins and flavin mononucleotide (FMN), are useful models to investigate the mechanism of protein/flavin recognition. In this respect, only available crystal structure an apoflavodoxin (that from Anabaena) showed a closed isoalloxazine pocket presence bound phosphate ion, which posed many questions on recognition potential physiological role exerted by ions. To address these issues we report here X‐ray pathogen Helicobacter pylori....
Abstract The three‐dimensional structures of K72E, K75R, K75S, K75Q, and K75E Anabaena Ferredoxin‐NADP + reductase (FNR) mutants have been solved, particular structural details these used to assess the role played by residues 72 75 in optimal complex formation electron transfer (ET) between FNR its protein redox partners Ferredoxin (Fd) Flavodoxin (Fld). Additionally, because there is no information available on interaction Fld, a model for FNR:Fld has also produced based previously reported...
Analysis of the crystal structure NifF from Rhodobacter capsulatus and its homologues reported so far reflects existence unique structural features in nif flavodoxins: a leucine at re face isoalloxazine, an eight-residue insertion C-terminus 50’s loop remarkable difference electrostatic potential surface with respect to non-nif flavodoxins. A phylogenetic study on 64 sequences 52 bacterial species revealed four clusters, including different functional prototypes, correlating previously...
Data pathologies caused by effects such as diffraction anisotropy and translational noncrystallographic symmetry (tNCS) can dramatically complicate the solution of crystal structures macromolecules. Such problems were encountered in determining structure a mutant form Rab27a, member Rab GTPases. Mutant Rab27a constructs that crystallize free designed for use discovery drugs to reduce primary tumour invasiveness metastasis. One construct, hRab27a Mut , crystallized within 24 h diffracted 2.82...
A novel Rab27A construct enables elucidation of covalent ligand binding, paving the way for structure-guided approaches against this challenging target.
Pseudomonas aeruginosa is a Gram-negative opportunistic bacterial pathogen that can cause chronic infection of the lungs cystic fibrosis patients. Chaperone-usher systems in P. are known to translocate and assemble adhesive pili on surface contribute biofilm formation within host. Here, we report crystal structure tip adhesion subunit CupB6 from cupB1-6 gene cluster. The domain connected pilus via N-terminal donor strand main CupB1. Although bears structural features similar other CU...
LytC, one of the major autolysins from human pathogen Streptococcus pneumoniae, has been crystallized as needles by hanging-drop technique using 10%(w/v) PEG 3350 precipitant and 10 mM HEPES pH 7.5. LytC crystals were quickly soaked in mother liquor containing 2 complex Gd-HPDO3A to produce derivatized (LytCGd-HPDO3A). Both native isomorphous LytCGd-HPDO3A flash-cooled a nitrogen flow at 120 K prior X-ray data collection an in-house Enraf–Nonius rotating-anode generator (λ = 1.5418 Å) MAR345...