1ne6
Crystal structure of Sp-cAMP binding R1a subunit of cAMP-dependent protein kinase
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OverviewOverview
Cyclic adenosine 5'-monophosphate (cAMP) is an ancient signaling molecule, and in vertebrates, a primary target for cAMP is cAMP-dependent protein, kinase (PKA). (R(p))-adenosine 3',5'-cyclic monophosphothioate, ((R(p))-cAMPS) and its analogues are the only known competitive inhibitors, and antagonists for cAMP activation of PKA, while (S(p))-adenosine, 3',5'-cyclic monophosphothioate ((S(p))-cAMPS) functions as an agonist., The crystal structures of a Delta(1-91) deletion mutant of the RIalpha, regulatory subunit of PKA bound to (R(p))-cAMPS and (S(p))-cAMPS were, determined at 2.4 and 2.3 A resolution, respectively. While the structures, are similar to each other and to the crystal structure of RIalpha bound to, cAMP, differences in the dynamical properties of the protein when, (R(p))-cAMPS is bound are apparent. The structures highlight the critical, importance of the exocyclic oxygen's interaction with the invariant, arginine in the phosphate binding cassette (PBC) and the importance of, this interaction for the dynamical properties of the interactions that, radiate out from the PBC. The conformations of the phosphate binding, cassettes containing two invariant arginine residues (Arg209 on domain A, and Arg333 on domain B) are somewhat different due to the sulfur, interacting with this arginine. Furthermore, the B-site ligand together, with the entire domain B show significant differences in their overall, dynamic properties in the crystal structure of Delta(1-91) RIalpha, complexed with (R(p))-cAMPS phosphothioate analogue ((R(p))-RIalpha), compared to the cAMP- and (S(p))-cAMPS-bound type I and II regulatory, subunits, based on the temperature factors. In all structures, two, structural solvent molecules exist within the A-site ligand binding, pocket; both mediate water-bridged interactions between the ligand and the, protein. No structured waters are in the B-site pocket. Owing to the, higher resolution data, the N-terminal segment (109-117) of the RIalpha, subunit can also be traced. This strand forms an intermolecular, antiparallel beta-sheet with the same strand in an adjacent molecule and, implies that the RIalpha subunit can form a weak homodimer even in the, absence of its dimerization domain.
About this StructureAbout this Structure
1NE6 is a Single protein structure of sequence from Bos taurus with SP1 as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of RIalpha subunit of cyclic adenosine 5'-monophosphate (cAMP)-dependent protein kinase complexed with (Rp)-adenosine 3',5'-cyclic monophosphothioate and (Sp)-adenosine 3',5'-cyclic monophosphothioate, the phosphothioate analogues of cAMP., Wu J, Jones JM, Nguyen-Huu X, Ten Eyck LF, Taylor SS, Biochemistry. 2004 Jun 1;43(21):6620-9. PMID:15157095
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