A5090133072- Methane Hydrates and Related Phenomena
- SARS-CoV-2 and COVID-19 Research
- Earthquake Detection and Analysis
- Seismic Waves and Analysis
- Enzyme Structure and Function
- Connexins and lens biology
- SARS-CoV-2 detection and testing
- Protein Structure and Dynamics
- CRISPR and Genetic Engineering
- Bacillus and Francisella bacterial research
- Bacteriophages and microbial interactions
- COVID-19 Clinical Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Yersinia bacterium, plague, ectoparasites research
- Biochemical and Molecular Research
- Animal Virus Infections Studies
- RNA and protein synthesis mechanisms
- Enzyme Production and Characterization
- Biofuel production and bioconversion
- Photosynthetic Processes and Mechanisms
- Bacterial Genetics and Biotechnology
- Genetics, Bioinformatics, and Biomedical Research
- Viral Infections and Outbreaks Research
- Magnetic and Electromagnetic Effects
University of British Columbia
2020-2022
Centre for Cellular and Molecular Biology
2012-2019
Council of Scientific and Industrial Research
2011-2014
The newly reported Omicron variant is poised to replace Delta as the most prevalent SARS-CoV-2 across world. Cryo-EM structural analysis of spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 R498 RBD ACE2. These interactions appear compensate for other mutations such K417N known reduce binding affinity, resulting similar biochemical affinities variants. Neutralization assays show that pseudoviruses displaying exhibit...
The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result several changes, including the N501Y mutation. We present 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure complex between ACE2 receptor and spike protein ectodomains that shows Y501 inserted into cavity at binding interface near Y41 ACE2. This additional interaction provides structural explanation for increased affinity mutant, likely...
The Delta and Kappa variants of SARS-CoV-2 co-emerged in India late 2020, with the variant underlying resurgence COVID-19, even countries high vaccination rates. In this study, we assess structural biochemical aspects viral fitness for these two using cryo-electron microscopy (cryo-EM), ACE2-binding antibody neutralization analyses. Both demonstrate escape antibodies targeting N-terminal domain, an important immune hotspot neutralizing epitopes. Compared to wild-type lineages, spike proteins...
The recently emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Beta (B.1.351) and Gamma (P.1) variants of concern (VoCs) include a key mutation (N501Y) found in the Alpha (B.1.1.7) variant that enhances affinity spike protein for its receptor, angiotensin-converting enzyme 2 (ACE2). Additional mutations are these at residues 417 484 appear to promote antibody evasion. In contrast, Epsilon (B.1.427/429) lack N501Y yet exhibit We have engineered proteins express receptor...
Abstract Mutations in the spike glycoproteins of SARS-CoV-2 variants concern have independently been shown to enhance aspects protein fitness. Here, we describe an antibody fragment (V H ab6) that neutralizes all major including recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode binding revealed by cryo-EM studies. Further, provide comparative analysis mutational effects within previously variant spikes identify structural role mutations NTD RBD evading neutralization....
The newly reported Omicron variant is poised to replace Delta as the most rapidly spread SARS-CoV-2 across world. Cryo-EM structural analysis of spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 R498 RBD ACE2. These interactions appear compensate for other mutations such K417N known reduce binding affinity, explaining our finding similar biochemical affinities variants. Neutralization assays show that pseudoviruses...
Abstract The recently reported “UK variant” of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result several changes, including the N501Y mutation. We present 2.9-Å resolution cryo-EM structure complex between ACE2 receptor and spike protein ectodomains that shows Y501 inserted into cavity at binding interface near Y41 ACE2. additional interactions in increased affinity for mutant, accounting its infectivity. However, this mutation does not large...
The folding and unfolding of structurally similar proteins belonging to a family have long been focus investigation the structure-(un)folding relationship. Such studies are yet reach consensus about whether domains follow common or different pathways. Members βγ-crystallin superfamily, which consists with limited sequence similarity from diverse life forms spanning microbes mammals, form an appropriate model system for exploring this relationship further. We selected new member, Crybg3_D3,...
Malaria is a devastating disease caused by protozoan parasite. It affects over 300 million individuals and results in 400 000 deaths annually, most of whom are young children under the age five. Hexokinase, first enzyme glucose metabolism, plays an important role infection process represents promising target for therapeutic intervention. Here, cryo-EM structures two conformational states Plasmodium vivax hexokinase (PvHK) reported at resolutions ∼3 Å. shown that unlike other known...
βγ-Crystallins are important constituents of the vertebrate eye lens, whereas in microbes, they prevalent as Ca2+-binding proteins. In archaea, βγ-crystallins conspicuously confined to two methanogens, viz., Methanosaeta and Methanosarcina. One these, i.e., M-crystallin from Methanosarcina acetivorans, has been shown be a typical βγ-crystallin. Here, with aid high-resolution crystal structure isothermal titration calorimetry, we report that "Methallin", βγ-crystallin thermophila, is...
Abstract The Delta and Kappa variants of SARS-CoV-2 co-emerged in India late 2020, with the variant underlying resurgence COVID-19, even countries high vaccination rates. In this study, we assess structural biochemical aspects viral fitness for these two using cryo-electron microscopy (cryo-EM), ACE2-binding antibody neutralization analyses. Both demonstrate escape antibodies targeting N-terminal domain, an important immune hotspot neutralizing epitopes. Compared to wild-type lineages, spike...
We have biochemically and structurally characterized a novel glucanase from the less studied GH64 family in bacterium significant for fermentation of carbohydrates into biofuels. This enzyme displays peculiar property being distally modulated by Ca 2+ via assistance neighboring βγ-crystallin domain, likely through changes domain interface. In addition, this is found to be optimized functioning an acidic environment, which line with possibility its involvement biofuel production. Multiple...
Summary The recently emerged SARS-CoV-2 South African (B. 1.351) and Brazil/Japan (P.1) variants of concern (VoCs) include a key mutation (N501Y) found in the UK variant that enhances affinity spike protein for its receptor, ACE2. Additional mutations are these at residues 417 484 appear to promote antibody evasion. In contrast, Californian VoCs (B.1.427/429) lack N501Y mutation, yet exhibit We engineered proteins express RBD VoC either isolation, or different combinations, analyzed effects...
Abstract Mutations in the spike glycoproteins of SARS-CoV-2 variants concern have independently been shown to enhance aspects protein fitness. Here, we report discovery a novel antibody fragment (V H ab6) that neutralizes all major variants, with unique mode binding revealed by cryo-EM studies. Further, provide comparative analysis mutational effects within variant spikes and identify structural role mutations NTD RBD evading neutralization. Our shows highly mutated Gamma N-terminal domain...
We describe a set of proteins in which βγ-crystallin domain pairs with an Ig-like domain, and are confined to microbes, like bacteria, slime molds fungi. DdCAD-1 (Ca2+ -dependent cell adhesion molecule-1) abundant perithecial protein (APP) represent this class molecules. Using the crystal structure APP-NTD (N-terminal APP), we its mode Ca2+ binding provide generalized theme for correct identification -binding site within As common feature, one two sites is non-functional domains these...