PerspectiveBiochemistry

Allosteric Regulation of Nucleotidyl Cyclases: An Emerging Pharmacological Target

Science Signaling  04 Sep 2012:
Vol. 5, Issue 240, pp. pe37
DOI: 10.1126/scisignal.2003466

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Abstract

Adenylyl cyclases (ACs) and guanylyl cyclases (GCs) produce the second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate, respectively. ACs and GCs are differentially regulated by intercellular signaling molecules and are implicated in various disease states, including cardiovascular diseases, aging, pain, and neuropsychiatric ailments. Hence, ACs and GCs constitute interesting drug targets. Because the catalytic sites of these enzymes are highly conserved, it is difficult to achieve isoform specificity. However, studies have provided evidence for the notion that regulatory allosteric domains in the vicinity of the catalytic site provide new opportunities for pharmacological intervention. Here, we summarize the current status of such research and discuss future directions in this exciting field.

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