A5011736665- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- Chemical Synthesis and Analysis
- RNA and protein synthesis mechanisms
- Histone Deacetylase Inhibitors Research
- HIV/AIDS drug development and treatment
- Genetic Neurodegenerative Diseases
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Protein Structure and Dynamics
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Hypoxia, and Metabolism
- Pharmacogenetics and Drug Metabolism
- Multiple Myeloma Research and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Sirtuins and Resveratrol in Medicine
University of Toronto
2016-2025
Structural Genomics Consortium
2016-2025
Ontario Institute for Cancer Research
2024
Princess Margaret Cancer Centre
2024
University Health Network
2024
Central China Normal University
2021
Pennsylvania State University
2007
University of British Columbia
2003
Histone deacetylases (HDACs) are protein that play a role in repression of gene transcription and emerging targets cancer therapy. Here, we characterize the structure enzymatic activity catalytic domain human HDAC7 (cdHDAC7). Although normally exists as part multiprotein complex, show cdHDAC7 has low level deacetylase which can be inhibited by known HDAC inhibitors. The crystal structures its complexes with two hydroxamate inhibitors first class IIa HDACs demonstrate significant differences...
The human cytosolic sulfotransfases (hSULTs) comprise a family of 12 phase II enzymes involved in the metabolism drugs and hormones, bioactivation carcinogens, detoxification xenobiotics. Knowledge structural mechanistic basis substrate specificity activity is crucial for understanding steroid hormone metabolism, drug sensitivity, pharmacogenomics, response to environmental toxins. We have determined crystal structures five hSULTs which information was lacking, screened nine binding toward...
Abstract SETDB1 is an essential H3K9 methyltransferase involved in silencing of retroviruses and gene regulation. We show here that its triple Tudor domain (3TD) specifically binds to doubly modified histone H3 containing K14 acetylation K9 methylation. Crystal structures 3TD complex with H3K14ac/K9me peptides reveal peptide binding K14ac recognition occurs at the interface between domains (TD) TD2 TD3. Structural biochemical data demonstrate a pocket switch mechanism code reading, because...
The COVID-19 pandemic has clearly brought the healthcare systems worldwide to a breaking point, along with devastating socioeconomic consequences. SARS-CoV-2 virus, which causes disease, uses RNA capping evade human immune system. Nonstructural protein (nsp) 14 is one of 16 nsps in and catalyzes methylation viral at N7-guanosine cap formation process. To discover small-molecule inhibitors nsp14 methyltransferase (MTase) activity, we developed employed radiometric MTase assay screen library...
The human arylamine N-acetyltransferases NAT1 and NAT2 play an important role in the biotransformation of a plethora aromatic amine hydrazine drugs. They are also able to participate bioactivation several known carcinogens. Each these enzymes is genetically variable populations, polymorphisms NAT genes have been associated with various cancers. Here we solved high resolution crystal structures NAT2, including complex irreversible inhibitor 2-bromoacetanilide, active site mutant, CoA, refined...
The crystal structures of two ternary complexes human spermine synthase (EC 2.5.1.22), one with 5′-methylthioadenosine and spermidine the other spermine, have been solved. They show that enzyme is a dimer identical subunits. Each monomer has three domains: C-terminal domain, which contains active site similar in structure to synthase; central domain made up four β-strands; an N-terminal remarkable structural similarity S-adenosylmethionine decarboxylase, forms aminopropyl donor substrate....
Aminopropyltransferases transfer aminopropyl groups from decarboxylated S-adenosylmethionine to amine acceptors, forming polyamines. Structural and biochemical studies have been carried out with the human spermidine synthase, which is highly specific for putrescine as acceptor, Thermotoga maritima prefers but more tolerant of other substrates. Comparison structures synthase both substrates products known structure T. complexed a multisubstrate analogue inhibitor analysis properties...
Abstract Huntington’s disease results from expansion of a glutamine-coding CAG tract in the huntingtin (HTT) gene, producing an aberrantly functioning form HTT. Both wildtype and disease-state HTT hetero-dimer with HAP40 unknown functional relevance. We demonstrate vivo cell models that cellular abundance are coupled. Integrating data 2.6 Å cryo-electron microscopy structure, cross-linking mass spectrometry, small-angle X-ray scattering, modeling, we provide near-atomic-level view HTT, its...
Seven coronaviruses have infected humans (HCoVs) to-date. SARS-CoV-2 caused the current COVID-19 pandemic with well-known high mortality and severe socioeconomic consequences. MERS-CoV SARS-CoV epidemic of MERS SARS, respectively, respiratory symptoms significant fatality. However, HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43 cause illnesses less in most cases. All use RNA capping to evade immune systems humans. Two viral methyltransferases, nsp14 nsp16, play key roles are considered valuable...
The cyclic guanosine-3′,5′-monophosphate (cGMP)-dependent protein kinase (PKG) was identified >25 y ago; however, efforts to obtain a structure of the entire PKG enzyme or catalytic domain from any species have failed. In malaria parasites, cooperative activation triggers crucial developmental transitions throughout complex life cycle. We determined cGMP-free crystallographic structures Plasmodium falciparum and vivax , revealing how key structural components, including an N-terminal...
BACKGROUND. The role of humoral immunity in COVID-19 is not fully understood, owing, large part, to the complexity antibodies produced response SARS-CoV-2 infection. There a pressing need for serology tests assess patient-specific antibody and predict clinical outcome.