A5059202039- RNA modifications and cancer
- RNA Research and Splicing
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Cancer-related gene regulation
- Metabolomics and Mass Spectrometry Studies
- Legionella and Acanthamoeba research
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
- Plant biochemistry and biosynthesis
- Cardiac Ischemia and Reperfusion
- Heme Oxygenase-1 and Carbon Monoxide
- Cardiac Arrest and Resuscitation
- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
- 14-3-3 protein interactions
- ATP Synthase and ATPases Research
- Epigenetics and DNA Methylation
- Horticultural and Viticultural Research
- Fermentation and Sensory Analysis
- Natural product bioactivities and synthesis
- SARS-CoV-2 detection and testing
- COVID-19 Clinical Research Studies
University of Dundee
2016-2025
Max Planck Society
2012
The CCR4–NOT complex plays a crucial role in post-transcriptional mRNA regulation eukaryotic cells. It catalyzes the removal of poly(A) tails, thereby repressing translation and committing mRNAs to decay. conserved core consists catalytic module comprising two deadenylases (CAF1/POP2 CCR4a/b) NOT module, which contains at least NOT1, NOT2 NOT3. NOT1 bridges interaction between modules therefore, acts as scaffold protein for assembly complex. Here, we present crystal structures CAF1-binding...
Maturation and translation of mRNA in eukaryotes requires the addition 7-methylguanosine cap. In vertebrates, cap methyltransferase, RNA guanine-7 methyltransferase (RNMT), has an activating subunit, RNMT-Activating Miniprotein (RAM). Here we report first crystal structure human RNMT complex with activation domain RAM. A relatively unstructured negatively charged RAM binds to a positively surface groove on RNMT, distal active site. This results stabilisation lobe which co-evolved is required...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents a significant threat to human health. Despite its similarity related coronaviruses, there are currently no specific treatments for COVID-19 infection, and therefore is an urgent need develop therapies this future coronavirus outbreaks. Formation of the cap at 5′ end viral RNA has been shown help coronaviruses evade host defenses. Nonstructural protein 14 (nsp14) responsible N7-methylation guanosine in coronaviruses. This...
The maturation of the RNA cap involving guanosine N-7 methylation, catalyzed by HsRNMT (RNA guanine-7 methyltransferase)-RAM guanine-N7 methyltransferase activating subunit) complex, is currently under investigation as a novel strategy to combat PIK3CA mutant breast cancer. However, development effective drugs hindered limited understanding enzyme's mechanism and lack small molecule inhibitors. Following elucidation HsRNMT-RAM molecular mechanism, we report biophysical characterization two...
Abstract Identification and assessment of novel targets is essential to combat drug resistance in the treatment HIV/AIDS. HIV Capsid (HIV‐CA), protein playing a major role both early late stages viral life cycle, has emerged as an important target. We have applied NMR fragment screening platform identified molecules that bind N ‐terminal domain (NTD) HIV‐CA at site close interface with C (CTD). Using X‐ray crystallography, we been able obtain crystal structures identify binding mode these...
The maturation of the RNA cap involving guanosine N-7 methylation, catalyzed by HsRNMT (RNA guanine-7 methyltransferase)-RAM guanine-N7 methyltransferase activating subunit) complex, is currently under investigation as a novel strategy to combat PIK3CA mutant breast cancer. However, development effective drugs hindered limited understanding enzyme's mechanism and lack small molecule inhibitors. Following elucidation HsRNMT-RAM molecular mechanism, we report biophysical characterization two...
Abstract Identification and assessment of novel targets is essential to combat drug resistance in the treatment HIV/AIDS. HIV Capsid (HIV-CA), protein playing a major role both early late stages viral life cycle, has emerged as an important target. We have applied NMR fragment screening platform identified molecules that bind N -terminal domain (NTD) HIV-CA at site close interface with C (CTD). Using X-ray crystallography, we been able obtain crystal structures identify binding mode these...