A5007949259- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Lipid Membrane Structure and Behavior
- Bacterial Genetics and Biotechnology
- Cardiomyopathy and Myosin Studies
- Bacteriophages and microbial interactions
- Signaling Pathways in Disease
- Antimicrobial Peptides and Activities
- Ion channel regulation and function
- Monoclonal and Polyclonal Antibodies Research
- Antibiotic Resistance in Bacteria
- Glycosylation and Glycoproteins Research
- Biochemical and Molecular Research
- Enzyme Catalysis and Immobilization
- Protein purification and stability
- Metabolomics and Mass Spectrometry Studies
- Magnetic Properties and Applications
- Amino Acid Enzymes and Metabolism
- Advanced NMR Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
- Infant Nutrition and Health
- Escherichia coli research studies
- Biochemical and Structural Characterization
- Enzyme function and inhibition
University of Alberta
2016-2025
General Department of Preventive Medicine
2014
University of California San Francisco Medical Center
2014
University of Toronto
1998-2006
Ontario Institute for Cancer Research
1998-2002
University of Calgary
1998-2002
Hospital for Sick Children
2002
Massachusetts Institute of Technology
2002
Canada Research Chairs
2002
University of Massachusetts Chan Medical School
1991
A comparison of HSQC and HMQC pulse schemes for recording 1H−13C correlation maps protonated methyl groups in highly deuterated proteins is presented. It shown that can be as much a factor 3 more sensitive than their counterparts the sensitivity gains result from TROSY effect involves cancellation intra-methyl dipolar relaxation interactions. spectra are recorded on U-[15N,2H], Ileδ1-[13C,1H] samples (i) malate synthase G, 723 residue protein, at 37 5 °C, (ii) protease ClpP, comprising 14...
The bacterial outer membrane enzyme PagP transfers a palmitate chain from phospholipid to lipid A. In number of pathogenic Gram-negative bacteria, confers resistance certain cationic antimicrobial peptides produced during the host innate immune response. global fold Escherichia coli was determined in both dodecylphosphocholine and n -octyl-β- d -glucoside detergent micelles using solution NMR spectroscopy. consists an eight-stranded anti-parallel β-barrel preceded by amphipathic α helix. is...
The solution structure of bovine lactoferricin (LfcinB) has been determined using 2D 1H NMR spectroscopy. LfcinB is a 25-residue antimicrobial peptide released by pepsin cleavage lactoferrin, an 80 kDa iron-binding glycoprotein with many immunologically important functions. reveals somewhat distorted antiparallel β-sheet. This contrasts the X-ray in which residues 1−13 (of LfcinB) form α-helix. Hence, this region B appears able to adopt helical or sheetlike conformation, similar what...
The highly conserved, 300-kDa cylindrical protease ClpP is an important component of the cellular protein quality machinery. It consists 14 subunits arranged into two heptameric rings that enclose a large chamber containing active sites. associates with ClpX and ClpA ATPases unfold translocate substrates catalytic through axial pores located at both ends cylinder. Although pathway substrate delivery well established, product release unknown. Here, we use recently developed transverse...
Tritrpticin is a member of the cathelicidin family, group diverse antimicrobial peptides found in neutrophil granules. The three Trp and four Arg residues sequence VRRFPWWWPFLRR make this Trp-rich cationic peptide. structure tritrpticin bound to membrane-mimetic sodium dodecyl sulfate micelles has been determined using conventional two-dimensional NMR methods. It forms two adjacent turns around Pro residues, distinct fold for peptide-membrane interaction. first turn involves 4-7, followed...
Lactoferricin B (LfcinB) is a 25‐residue antimicrobial peptide released from bovine lactoferrin upon pepsin digestion. The center of LfcinB consists six residues (RRWQWR‐NH 2 ), and it possesses similar bactericidal activity to LfcinB. structure the six‐residue bound sodium dodecyl sulfate (SDS) micelles has been determined by NMR spectroscopy molecular dynamics refinement. adopts well defined amphipathic when SDS with Trp sidechains separated Arg residues. Additional evidence demonstrates...
PhoPQ-activated gene P (PagP) is an integral membrane enzyme that transfers the sn -1 palmitate chain from phospholipid to lipopolysaccharide in Gram-negative bacteria. A recent x-ray crystallographic study established binds within a long cavity at center of PagP β barrel. The high mobility required permit substrate entry into central core barrel contrasts with need assemble well defined structure peripheral loops, where many key catalytic residues are located. To gain insight how dynamics...
Integrin adhesion receptors constitute a cell-signaling system whereby interactions in the small cytoplasmic domains of heterodimeric alpha- and beta-subunits provoke major functional alterations large extracellular domains. With two-dimensional NMR spectroscopy, we examined two synthetic peptides [alphaIIb((987)MWKVGFFKRNR) beta3((716)KLLITIHDRKEFAKFEEERARAKWD)] encompassing membrane-proximal regions domain motifs from platelet integrin complex alphaIotaIotabbeta3. These contain conserved...
Significance Protein–protein interactions typically involve some degree of induced fit, producing complementary surfaces that account for high affinity and specificity. However, there are increasingly more examples intrinsically disordered regions (IDRs) exert important biologic effects despite never attaining a rigid structure. Here we show how particularly region cardiac troponin I impacts the overall global conformation function its binding partner, C. This newly described role an IDR is...
Significance Transcription factor II D (TFIID) is a multiprotein complex that essential for gene transcription. Together, TATA binding protein-associated 1 (TAF1), the biggest TFIID subunit, and TAF7 form an important control point transcriptional initiation. Although current models suggest binds TAF1 to block its intrinsic histone acetyltransferase (HAT) activity, almost nothing known about molecular basis of TAF1–TAF7 (TAF1/7) interaction activity. Here, we report atomic structure yeast...
The rare metal element molybdenum functions as a cofactor in molybdoenzymes that are essential to life almost all living things. Molybdate can be captured by the periplasmic substrate-binding protein ModA of ModABC transport system bacteria. We demonstrate plays crucial roles growth, multiple metabolic pathways, and ROS tolerance Acinetobacter baumannii . Crystal structures molybdate-coordinated A. show noncanonical disulfide bond with conformational change between reduced oxidized states....
The topology of the bacterial outer-membrane enzyme, PagP, in dodecylphosphocholine micelles was studied by solution NMR using oxygen and water contacts as probes hydrophobicity topology. effects on amide protons were measured at an partial pressure 20 atm through paramagnetic contribution to relaxation rates associated with decay two-spin order. A significant gradation observed for backbone amides belonging transmembrane residues. These depend immersion depth, local hydrophobicity, steric...
Antimicrobial peptides are ubiquitously produced throughout nature. Many of these relatively short (6-50 residues) lethal towards bacteria and fungi, yet they display minimal toxicity mammalian cells. All the highly cationic hydrophobic. It is widely believed that act through nonspecific binding to biological membranes, even though exact nature interactions presently unclear. High-resolution nuclear magnetic resonance (NMR) has contributed greatly knowledge in this field, providing insight...