2QCS
A complex structure between the Catalytic and Regulatory subunit of Protein Kinase A that represents the inhibited state
Summary for 2QCS
| Entry DOI | 10.2210/pdb2qcs/pdb |
| Related | 1APM 1NE4 1NE6 1RGS |
| Descriptor | cAMP-dependent protein kinase, alpha-catalytic subunit, cAMP-dependent protein kinase type I-alpha regulatory subunit, MANGANESE (II) ION, ... (9 entities in total) |
| Functional Keywords | cyclic adenosine monophosphate, camp-dependent protein kinase, pka holoenzyme, cyclic nucleotide binding domain, protein-protein interaction, conformational change, protein binding, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Mus musculus (house mouse) More |
| Cellular location | Cytoplasm . Isoform 2: Cell projection, cilium, flagellum : P05132 Cell membrane : P00514 |
| Total number of polymer chains | 2 |
| Total formula weight | 75151.43 |
| Authors | Kim, C.,Cheng, C.Y.,Saldanha, A.S.,Taylor, S.S. (deposition date: 2007-06-19, release date: 2007-11-06, Last modification date: 2023-08-30) |
| Primary citation | Kim, C.,Cheng, C.Y.,Saldanha, S.A.,Taylor, S.S. PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation. Cell(Cambridge,Mass.), 130:1032-1043, 2007 Cited by PubMed Abstract: Protein kinase A (PKA) holoenzyme is one of the major receptors for cyclic adenosine monophosphate (cAMP), where an extracellular stimulus is translated into a signaling response. We report here the structure of a complex between the PKA catalytic subunit and a mutant RI regulatory subunit, RIalpha(91-379:R333K), containing both cAMP-binding domains. Upon binding to the catalytic subunit, RI undergoes a dramatic conformational change in which the two cAMP-binding domains uncouple and wrap around the large lobe of the catalytic subunit. This large conformational reorganization reveals the concerted mechanism required to bind and inhibit the catalytic subunit. The structure also reveals a holoenzyme-specific salt bridge between two conserved residues, Glu261 and Arg366, that tethers the two adenine capping residues far from their cAMP-binding sites. Mutagenesis of these residues demonstrates their importance for PKA activation. Our structural insights, combined with the mutagenesis results, provide a molecular mechanism for the ordered and cooperative activation of PKA by cAMP. PubMed: 17889648DOI: 10.1016/j.cell.2007.07.018 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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