October 2, 2015

The yin and yang of COX-2

New findings add to the understanding of how the enzyme COX-2 works, which is critical to the development of COX-2-targeted anti-inflammatory drugs.

by Sanjay Mishra


The cyclooxygenase (COX) enzymes play important roles in the biosynthesis of prostaglandins, key signaling molecules that mediate fever, pain, and inflammation. Aspirin and other non-steroidal anti-inflammatory drugs work by blocking the COX enzymes, which exist in two flavors: always-expressed COX-1 and inflammation-inducible COX-2.

Understanding how COX-2 is regulated is crucial to understanding its role in inflammation and the development of better COX-2-targeted anti-inflammatory drugs.

In a study published in the Proceedings of the National Academy of Sciences, Lawrence Marnett, Ph.D., and colleagues demonstrate that although COX-2 is made of identical halves, each half has a different function.

One half carries out the initial steps leading to prostaglandin production, while the other half regulates the efficiency of this process.

Their study provides the first evidence that binding of substrates to the regulatory side of the enzyme affects the capacity of the other side to produce prostaglandins, and that this form of regulation is important in living cells.

This research was supported by the National Institutes of Health (grants CA089450, GM015431, CA151918), the National Science Foundation and the Edward P. Evans Foundation.

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