A5073712525- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Lipid Membrane Structure and Behavior
- Enzyme Structure and Function
- Advanced NMR Techniques and Applications
- Antibiotic Resistance in Bacteria
- Streptococcal Infections and Treatments
- Microbial Metabolic Engineering and Bioproduction
- Genomics and Chromatin Dynamics
- Enzyme Production and Characterization
- Advanced biosensing and bioanalysis techniques
- Animal Virus Infections Studies
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Antimicrobial Resistance in Staphylococcus
- Lipoproteins and Cardiovascular Health
- Glycosylation and Glycoproteins Research
- Mitochondrial Function and Pathology
- Neonatal and Maternal Infections
- Plant Virus Research Studies
- Biochemical and Structural Characterization
- Legume Nitrogen Fixing Symbiosis
- Hemoglobin structure and function
- Genomics and Phylogenetic Studies
University of Ottawa
2012-2023
Marie Curie
2009
Scripps Research Institute
2002-2008
Steacie Institute for Molecular Sciences
2007
Hospital for Sick Children
1996-2002
University of Toronto
1998-2002
Canada Research Chairs
2001
Proline is established as a potent breaker of both alpha-helical and beta-sheet structures in soluble (globular) proteins. Thus, the frequent occurrence Pro residue putative transmembrane helices integral membrane proteins, particularly transport presents structural dilemma. We propose that this phenomenon results from fact propensity given amino acid may be altered to conform changes imposed by molecular environment. To test hypothesis on proline, we synthesized model peptides generic...
Structural plasticity of enzymes dictates their function. Yet, our ability to rationally remodel enzyme conformational landscapes tailor catalytic properties remains limited. Here, we report a computational procedure for tuning that is based on multistate design hinge-mediated domain motions. Using this method, redesign the landscape natural aminotransferase preferentially stabilize less populated but reactive conformation and thereby increase efficiency with non-native substrate, resulting...
Abstract Studies that focus on packing interactions between transmembrane (TM) helices in membrane proteins would greatly benefit from the ability to investigate their association and multi‐spanning TM domains. However, production, purification, characterization of such units have been impeded by high intrinsic hydrophobicity. We describe polar tagging approach biophysical analysis segment peptides, where incorporation residues suitable type number at one or both peptide N‐ C‐termini can...
Rhomboid proteins comprise the largest class of intramembrane protease known, being conserved from bacteria to humans. The functional status these proteases is typically assessed through direct or indirect detection peptide cleavage products. Although assays can report on ability a rhomboid catalyze bond cleavage, differences in measured hydrolysis rates reflect changes structure and activity catalytic residues, as well substrate access active site. Here we show that highly reactive...
MinE is required for the dynamic oscillation of Min proteins that restricts formation cytokinetic septum to midpoint cell in gram negative bacteria. Critical this MinD-binding by stimulate MinD ATP hydrolysis, a function had been assigned first ∼30 residues MinE. Previous models based on structure an autonomously folded dimeric C-terminal fragment suggested N-terminal domain freely accessible interactions with MinD. We report here solution NMR full-length dimer from Neisseria gonorrhoeae ,...
Abstract Phosphatidylinositol kinases (PIKs) are key enzymatic regulators of membrane phospholipids and environments that control many aspects cellular function, from signal transduction to secretion, through the Golgi apparatus. Here, we have developed a photoreactive “clickable” probe, PIK‐BPyne, report activity PIKs. We investigated selectivity efficiency probe both inhibit label PIKs, compared PIK‐BPyne wortmannin activity‐based also known target found can act as an effective in situ for...
Do the truncated LL-37 peptides, GI-20 and GF-17, have spermicidal activity microbicidal effects on sexually transmitted infection (STI) pathogen Neisseria gonorrhoeae with equivalent potency to LL-37?
Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a ligand of low-density lipoprotein (LDL) receptor (LDLR) that promotes LDLR degradation in late endosomes/lysosomes. In human plasma, 30-40% PCSK9 bound to LDL particles; however, the physiological significance this interaction remains unknown. binding vitro requires disordered N-terminal region PCSK9's prodomain. Here, we report peptides corresponding predicted amphipathic α-helix prodomain N terminus adopt helical structure...
The bacterial cell division regulators MinD and MinE together with the inhibitor MinC localize to membrane in concentrated zones undergoing coordinated pole-to-pole oscillation help ensure that cytokinetic septum forms only at mid-cell position. This dynamic localization is driven by MinD-catalyzed ATP hydrolysis, stimulated interactions MinE's anti-MinCD domain. domain buried 6-β–stranded "closed" structure, but liberated for MinD, giving rise a 4-β–stranded "open" structure through an...
Rhomboids comprise a broad family of intramembrane serine proteases that are found in wide range organisms and participate diverse array biological processes. High-resolution structures the catalytic transmembrane domain Escherichia coli GlpG rhomboid have provided numerous insights help explain how hydrolytic cleavage can be achieved below membrane surface. Key to this observations hydrophobic dimensions may not sufficient completely span native lipid bilayer. This formed basis for model...
Eukaryotes have evolved complex cellular responses to double-stranded RNA. The quantities of short interfering RNA (siRNA) can be determined rapidly by using 96-well arrays the carnation Italian ringspot virus (CIRV) p19 protein, which binds siRNAs with nanomolar affinity and discriminates siRNA according length. Two compounds were found inhibit binding CIRV alkylating active-site cysteine residues (see diagram). Supporting information for this article is available on WWW under...