Columbia University scientists, in collaboration with researchers from Nimbus Therapeutics, have demystified a metabolic enzyme that could be the next major molecular target in cancer treatment.
The team has successfully determined the 3D structure of human ATP-citrate lyase (ACLY) — which plays a key role in cancer cell proliferation and other cellular processes — for the first time.
The findings, published April 3 in Nature, represent a first step in better understanding the enzyme in order to create effective molecular targeted therapies for patients.
While previous experiments have succeeded with fragments of the enzyme, the current work reveals the full structure of human ACLY at high resolution.
“ACLY is a metabolic enzyme that controls many processes in the cell, including fatty acid synthesis in cancer cells. By inhibiting this enzyme, hopefully we can control cancer growth,” said Liang Tong, William R. Kenan Jr. professor and department chair of Biological Sciences at Columbia and senior author of the study. “In addition, the enzyme has other roles, including cholesterol biosynthesis, so inhibitors against this enzyme could also be useful toward controlling cholesterol levels.”
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