Researchers identify enzyme that could be targeted to help body tackle LDL’s
Scientists from the University of Leicester and the University of California Los Angeles (UCLA) have announced a major advance towards developing drugs to tackle dangerous, or ‘bad’, cholesterol in the body.
Prof. John Schwabe
University of Leicester
Prof. of Structural Biology
They have filed two patents for developing targeted drugs that would act as a catalyst for lowering levels of ‘bad’ cholesterol. Two research papers published by the academics enhance the understanding of the regulation of low density lipoprotein (LDL) or “bad” cholesterol.
LDL, the so called ‘bad’ cholesterol, is often linked to medical problems like heart disease, stroke and clogged arteries.
In the body, cells in the liver produce an LDL receptor that binds LDL and removes it from the blood, thereby lowering cholesterol levels.
The scientists have characterised an enzyme called IDOL that plays a key role in regulating the amount of LDL receptor available to bind with ‘bad’ cholesterol. Therefore targeting the enzyme with drugs could increase the levels of LDL receptors present, thus lowering circulating cholesterol in humans.
Professor John Schwabe, Head of Biochemistry at the University of Leicester, said: “Development of a drug that interferes with IDOL’s activity could help lower levels of LDL. Our research has greatly enhanced our understanding of this important process.”
Prof John Schwabe, Dr Ben Goult and Dr Louise Fairall at the University of Leicester in collaboration with the University of California Los Angeles (UCLA) published their research in the top research journals: Genes & Development and the Proceedings of the National Academy of Science (PNAS). The research was funded by The Wellcome Trust, the NIH and the Howard Hughes Medical Institute.
The study published in Genes & Development announced the first atomic structural information on IDOL and identified the E2 ligase, UBE2D that works with IDOL to degrade the LDL receptor.
In the second research article published in PNAS, the team elucidated the molecular basis for the stringent specificity of IDOL for the LDL receptor.
Professor Schwabe added: “Remarkably, IDOL only targets three proteins for degradation (all lipoprotein receptors) and this research paper greatly enhances our understanding of this specificity and identifies key residues involved in mediating this interaction.”
“A potential future drug that targets IDOL could be prescribed in conjunction with statin drugs, which also cut cholesterol levels by increasing production of the LDL receptor and these two studies make considerable headway towards this.”