Researchers have mapped the molecular structure of a metabolic enzyme important to cancer development, which could offer a new target for cancer treatment, according to Science Daily. Called ATP-citrate lyase, scientists did not clearly understand its three-dimensional structure until now. The enzyme could offer a new focus for research into targeted cancer therapy, which aims to use drugs to block the effects of molecules within cancer cells that help them grow and proliferate throughout the body.

According to Professor Liang Tong, the study’s senior author and department chair of Biological Sciences at Columbia University:

“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. In addition, the enzyme has other roles, including cholesterol biosynthesis, so inhibitors against this enzyme could also be useful toward controlling cholesterol levels.”

Prior research has shown that the enzyme is overexpressed in some forms of cancer, and that inhibiting ACLY stops cancer cells from dividing and multiplying. A detailed understanding of the molecular architecture will help researchers develop drugs to inhibit the enzyme.

The researchers used an imaging technique called cryogenic electron microscopy (cryo-EM) to analyze the enzyme’s structure. The technique allows researchers to use an electron microscope to perform high-resolution imaging of frozen biological specimens. Jacques Dubochet, Joachim Frank and Richard Henderson won the 2017 Nobel Prize in Chemistry for the development of this imaging technique.

The research was published in the journal Nature on Wednesday, by a partnership between the Columbia scientists and researchers from Nimbus Therapeutics, a biotechnology company.

“This work is a major contribution to the scientific literature, and a remarkable demonstration of the potential of cryo-EM in drug discovery,” Tong said. “Together, we’ve demonstrated how combining computational insights with cutting-edge tools like cryo-EM may spark significant progress in cancer and metabolic disease research.”

“This paper is a terrific example of how our work at Nimbus combines cutting-edge technology, computational approaches and deep drug discovery experience to generate new scientific insights,” according to Nimbus CEO Jeb Keiper. “We’re excited to continue collaborating with experts as we interrogate new targets and deepen our pipeline of therapies.”


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