A5024213541- Protein Structure and Dynamics
- Enzyme Structure and Function
- Metabolomics and Mass Spectrometry Studies
- Platelet Disorders and Treatments
- Blood properties and coagulation
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Molecular spectroscopy and chirality
- Blood groups and transfusion
University College London
2019-2020
Institute of Structural and Molecular Biology
2019-2020
Transnational Press London
2019
Abstract Histone deacetylases (HDACs) are key enzymes in epigenetics and important drug targets cancer biology. Whilst it has been established that HDACs regulate many cellular processes, far less is known about the regulation of these themselves. Here, we show HDAC8 allosterically regulated by shifts populations between exchanging states. An inactive state identified, which stabilised a range mutations resembles sparsely-populated equilibrium with active HDAC8. Computational models states...
Whether recent updates and new releases of atomistic force fields can model the structural dynamical properties proteins containing both folded partially disordered domains is still unclear. To address this fundamental question, we tested eight recently released against our set nuclear magnetic resonance (NMR) observables for a complex medically relevant system, major factor VIII binding region on von Willebrand factor. This biomedically important comprises structured domain. By using an...
Abstract Side chains cover protein surfaces and are fundamental to processes as diverse substrate recognition, folding enzyme catalysis. However, characterisation of side-chain motions has so far been restricted small proteins methyl-bearing side chains. Here we present a class methods, based on 13 C-detected NMR spectroscopy, more generally quantify interactions in medium-to-large proteins. A single, uniformly isotopically labelled sample is sufficient characterise the six different amino...
A framework is presented to derive the conformational sampling of isoleucine side chains from nuclear magnetic resonance <sup>13</sup>C chemical shifts.