3FHI

Crystal structure of a complex between the catalytic and regulatory (RI{alpha}) subunits of PKA

Replaces:  1U7E

Summary for 3FHI

• Entry DOI: 10.2210/pdb3fhi/pdb
• Descriptor: cAMP-dependent protein kinase catalytic subunit alpha, cAMP-dependent protein kinase type I-alpha regulatory subunit, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: camp, camp dependent protein kinase, protein-protein complex, amp-pnp, protein kinase regulation, nucleotide binding, protein kinase activity, protein serine/threonine kinase activity, camp-dependent protein kinase activity, protein binding, atp binding, kinase activity, transferase activity, atp-binding, kinase, lipoprotein, myristate, nucleotide-binding, nucleus, phosphoprotein, serine/threonine-protein kinase, transferase, camp-binding
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm . Isoform 2: Cell projection, cilium, flagellum : P05132; Cell membrane : P00514
• Total number of polymer chains: 2
• Total formula weight: 58580.89

Authors

Kim, C. (deposition date: 2008-12-09, release date: 2009-04-14, Last modification date: 2024-10-30)

Primary citation

Kim, C.,Xuong, N.H.,Taylor, S.S.
Crystal structure of a complex between the catalytic and regulatory (RIalpha) subunits of PKA.
Science, 307:690-696, 2005

PubMed Abstract: The 2.0-angstrom structure of the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) catalytic subunit bound to a deletion mutant of a regulatory subunit (RIalpha) defines a previously unidentified extended interface. The complex provides a molecular mechanism for inhibition of PKA and suggests how cAMP binding leads to activation. The interface defines the large lobe of the catalytic subunit as a stable scaffold where Tyr247 in the G helix and Trp196 in the phosphorylated activation loop serve as anchor points for binding RIalpha. These residues compete with cAMP for the phosphate binding cassette in RIalpha. In contrast to the catalytic subunit, RIalpha undergoes major conformational changes when the complex is compared with cAMP-bound RIalpha. The inhibitor sequence docks to the active site, whereas the linker, also disordered in free RIalpha, folds across the extended interface. The beta barrel of cAMP binding domain A, which is the docking site for cAMP, remains largely intact in the complex, whereas the helical subdomain undergoes major reorganization.

PubMed: 15692043
DOI: 10.1126/science.1104607

Experimental method

X-RAY DIFFRACTION (2 Å)