A5066206406- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- FOXO transcription factor regulation
- Metal complexes synthesis and properties
- Mass Spectrometry Techniques and Applications
- Fish biology, ecology, and behavior
- interferon and immune responses
- Advanced biosensing and bioanalysis techniques
- Magnetism in coordination complexes
- Chemical Synthesis and Analysis
- Ichthyology and Marine Biology
- Trace Elements in Health
- Lanthanide and Transition Metal Complexes
- Protein Structure and Dynamics
- Sirtuins and Resveratrol in Medicine
- DNA Repair Mechanisms
- Enzyme Structure and Function
- Electrostatics and Colloid Interactions
- Protein Degradation and Inhibitors
- Aquaculture Nutrition and Growth
- RNA Research and Splicing
Institute of Cancer Research
2022-2024
King Abdullah University of Science and Technology
2020
Nanyang Technological University
2010-2017
Abstract Exploitation of drug–drug synergism and allostery could yield superior therapies by capitalizing on the immensely diverse, but highly specific, potential associated with biological macromolecular landscape. Here we describe a synergy mediated allosteric cross-talk in chromatin, whereby binding one drug alters activity second. We found two unrelated drugs, RAPTA-T auranofin, that synergistic killing cancer cells, which coincides substantially greater number chromatin adducts formed...
The haloarchaeon Halorubrum lacusprofundi is among the few polyextremophilic organisms capable of surviving in one most extreme aquatic environments on Earth, Deep Lake Antarctica (-18 °C to +11.5 and 21-28%, w/v salt content). Hence, H. has been proposed as a model for biotechnology astrobiology investigate potential life beyond Earth. To understand mechanisms that allow proteins adapt both salinity cold, we structurally (including X-ray crystallography molecular dynamics simulations)...
Abstract Lysine acetylation in histone tails is a key post-translational modification that controls transcription activation. Histone deacetylase complexes remove acetylation, thereby repressing and regulating the transcriptional output of each gene. Although these are drug targets crucial regulators organismal physiology, their structure mechanisms action largely unclear. Here, we present complete human SIN3B holo-complex with without substrate mimic. Remarkably, encircles contacts its...
Heavy metals have the potential to engage in strong bonding interactions and can thus function essential as well toxic or therapeutic capacities. We conducted crystallographic analyses of heavy cation binding nucleosome core particle found that Co2+ Ni2+ preferentially associate with DNA major groove, a sequence- conformation-dependent manner. Conversely, Rb+ Cs+ are bind only opportunistically minor groove elements DNA, particular at narrow AT dinucleotide sites. Furthermore, relative Mn2+...
Abstract Genes encoding the core cell cycle machinery are transcriptionally regulated by MuvB family of protein complexes in a cycle-specific manner. Complexes with transcription factors B-MYB and FOXM1 activate mitotic genes during proliferation. The mechanisms transcriptional regulation these still poorly characterised. Here, we combine biochemical analysis vitro reconstitution, structural cryo-electron microscopy cross-linking mass spectrometry, to functionally examine complexes. We find...
The proper control of mitosis depends on the ubiquitin-mediated degradation right mitotic regulator at time. This is effected by Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase that regulated Spindle Assembly Checkpoint (SAC). SAC prevents APC/C from recognising Cyclin B1, essential anaphase and cytokinesis inhibitor, until all chromosomes are attached to spindle. Once attached, B1 rapidly degraded enable chromosome segregation cytokinesis. We have a good understanding how...
Abstract Histone deacetylase complexes remove histone lysine acetylation, a key post-translational modification that activates transcription at each gene. Although these are drug targets and crucial regulators of organismal physiology, their structure mechanisms action largely unclear. Here, we present the first complete human SIN3B holo-complex with without substrate mimic. Remarkably, encircles contacts its allosteric basic patch thereby stimulating catalysis. A loop inserts into catalytic...
ABSTRACT The proper control of mitosis depends on the ubiquitin-mediated degradation right mitotic regulator at time. This is under anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase that regulated by Spindle Assembly Checkpoint (SAC). prevents APC/C from recognizing Cyclin B1, essential and cytokinesis inhibitor, until all chromosomes are attached to spindle. Once attached, B1 rapidly degraded enable chromosome segregation cytokinesis. We have a good understanding how SAC...