PT  - JOURNAL ARTICLE
AU  - Seifert, Roland
AU  - Beste, Kerstin Y.
TI  - Allosteric Regulation of Nucleotidyl Cyclases: An Emerging Pharmacological Target
AID  - 10.1126/scisignal.2003466
DP  - 2012 Sep 04
TA  - Science Signaling
PG  - pe37--pe37
VI  - 5
IP  - 240
4099  - http://stke.sciencemag.org/content/5/240/pe37.short
4100  - http://stke.sciencemag.org/content/5/240/pe37.full
SO  - Sci. Signal.2012 Sep 04; 5
AB  - 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.