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Sci. Signal., 4 September 2012
Vol. 5, Issue 240, p. ra65
[DOI: 10.1126/scisignal.2003253]


Editor's Summary

ATP Allosterically Regulates Guanylyl Cyclases
Adenylyl cyclase (AC) and guanylyl cyclase (GC) catalyze the generation of the cyclic nucleoside monophosphates cAMP and cGMP, respectively, which act as intracellular second messengers. ACs and GCs are implicated in various cardiovascular and metabolic diseases, making them pharmacological targets; however, because their catalytic sites are conserved, development of selective activators and inhibitors has been difficult (see the Perspective by Seifert and Beste). Through enzymatic analysis of wild-type and mutant GCs, Robinson and Potter showed that the binding of ATP to an allosteric site near the GTP-binding catalytic site of these enzymes enhanced their activity in response to GC ligands. Together, these data suggest that the allosteric site of GCs may provide a potential therapeutic target to modulate enzyme activity.

Citation: J. W. Robinson, L. R. Potter, Guanylyl Cyclases A and B Are Asymmetric Dimers That Are Allosterically Activated by ATP Binding to the Catalytic Domain. Sci. Signal. 5, ra65 (2012).

Read the Full Text

Structure/Activity Relationships of (M)ANT- and TNP-Nucleotides for Inhibition of Rat Soluble Guanylyl Cyclase {alpha}1{beta}1.
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