|
|
| Line 1: |
Line 1: |
| [[Image:1ne4.gif|left|200px]] | | {{Seed}} |
| | [[Image:1ne4.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_1ne4| PDB=1ne4 | SCENE= }} | | {{STRUCTURE_1ne4| PDB=1ne4 | SCENE= }} |
|
| |
|
| '''Crystal Structure of Rp-cAMP Binding R1a Subunit of cAMP-dependent Protein Kinase'''
| | ===Crystal Structure of Rp-cAMP Binding R1a Subunit of cAMP-dependent Protein Kinase=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15157095}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15157095 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_15157095}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 31: |
Line 35: |
| [[Category: R1a subunit]] | | [[Category: R1a subunit]] |
| [[Category: Rp-camp]] | | [[Category: Rp-camp]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:25:18 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:59:36 2008'' |