Biological complexity: enzyme complexity (Introduction)

by David Turell , Tuesday, April 26, 2016, 19:25 (3133 days ago) @ David Turell

Enzymes Are huge molecules which have specialized areas that lock in reactive areas. Without this lock and key arrangement necessary reactions could take hundreds of years to happen instead of the instantaneous time table of life:-https://www.sciencedaily.com/releases/2016/04/160425112511.htm-"The team, working under Professor John Schwabe from the University of Leicester's Department of Molecular and Cell Biology, focuses on understanding the structure and function of large protein complexes in the body that are involved in the regulation of gene expression called co-repressor complexes.-"These complexes contain histone deacetylase (HDAC) enzymes, which alter how DNA is packaged within cells.-***-"Professor Schwabe explained: "Previously our team had discovered that the activity of the enzymes in co-repressor complexes is regulated by a small molecule called inositol phosphate.-"'We wished to further understand the mechanism of enzyme activation by inositol phosphates and how substrate is recognised.-"'This work provides fundamental basic insights into the HDAC enzymes and may provide the basis for the development of drugs that are more specific and efficient. Ultimately, a greater understanding of how these enzymes work and how substrate interacts may lead to the development of better drugs."-"Working with collaborators from the University of Leicester's Department of Chemistry (Dr Andrew Jamieson's research group) and researchers at the University of Bath (Professor Barry Potter's research group), the team synthesised a number of unique tool compounds which allowed them to investigate how inositol phosphates and substrate bind to co-repressor complexes.-" They were then able to work out the specific features of inositol phosphates and how they bind to activate the HDAC enzyme. They then solved the crystal structure of a novel peptide inhibitor, which is based upon the enzymes' substrate, in complex with HDAC1: co-repressor. This not only gave insights into how substrate interacts with the enzyme but could also help to improve drug treatments for a variety of health issues. Taken together these results have shed light on the mechanism of activation by inositol phosphates."-Comment: Be sure to use the link and look at the diagram and the specialized binding pocket. How did chance evolution ever find this monster molecule?