Editing Cyclic nucleotide (section)

===Target Binding===
Cyclic nucleotides can be found in many different types of eukaryotic cells, including photo-receptor rods and cones, [[smooth muscle cells]] and [[liver cells]].  Cellular concentrations of cyclic nucleotides can be very low, in the 10<sup>−7</sup>[[molar concentration|M]] range, because [[metabolism]] and function are often localized in particular parts of the cell.<ref name="beavo">{{cite journal |vauthors=Beavo JA, Brunton LL |title=Cyclic nucleotide research -- still expanding after half a century |journal=Nat. Rev. Mol. Cell Biol. |volume=3 |issue=9 |pages=710–8 |date=September 2002 |pmid=12209131 |doi=10.1038/nrm911 |s2cid=33021271 }}</ref>  A highly conserved [[cyclic nucleotide-binding domain]] (CNB) is present in all proteins that bind cNMPs, regardless of their biological function.  The domain consists of a beta sandwich architecture, with the cyclic nucleotide binding pocket between the [[beta sheet]]s.  The binding of cNMP causes a conformational change that affects the protein's activity.<ref name="rehmann">{{cite journal |vauthors=Rehmann H, Wittinghofer A, Bos JL |title=Capturing cyclic nucleotides in action: snapshots from crystallographic studies |journal=Nat. Rev. Mol. Cell Biol. |volume=8 |issue=1 |pages=63–73 |date=January 2007 |pmid=17183361 |doi=10.1038/nrm2082 |s2cid=7216248 }}</ref>  There is also data to support a synergistic binding effect amongst multiple cyclic nucleotides, with cCMP lowering the effective concentration (EC<sub>50</sub>) of cAMP for activation of [[protein kinase A]] (PKA).<ref name="wolter">{{cite journal |vauthors=Wolter S, Golombek M, Seifert R |title=Differential activation of cAMP- and cGMP-dependent protein kinases by cyclic purine and pyrimidine nucleotides |journal=Biochem. Biophys. Res. Commun. |volume=415 |issue=4 |pages=563–6 |date=December 2011 |pmid=22074826 |doi=10.1016/j.bbrc.2011.10.093 }}</ref>