4NTS

Apo structure of the catalytic subunit of cAMP-dependent protein kinase

Summary for 4NTS

• Entry DOI: 10.2210/pdb4nts/pdb
• Related: 1ATP 1CMK 1J3H 1SYK 4DFY
• Descriptor: cAMP-dependent protein kinase catalytic subunit alpha, MYRISTIC ACID (2 entities in total)
• Functional Keywords: protein kinase fold, phosphoryl transferase, kinase, regulatory subunit of pka, pki, phosphorylation, transferase
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm . Isoform 2: Cell projection, cilium, flagellum : P05132
• Total number of polymer chains: 2
• Total formula weight: 81490.93

Authors

Bastidas, A.C.,Wu, J.,Taylor, S.S. (deposition date: 2013-12-02, release date: 2014-10-15, Last modification date: 2024-11-20)

Primary citation

Bastidas, A.C.,Wu, J.,Taylor, S.S.
Molecular Features of Product Release for the PKA Catalytic Cycle.
Biochemistry, 54:2-10, 2015

PubMed Abstract: Although ADP release is the rate limiting step in product turnover by protein kinase A, the steps and motions involved in this process are not well resolved. Here we report the apo and ADP bound structures of the myristylated catalytic subunit of PKA at 2.9 and 3.5 Å resolution, respectively. The ADP bound structure adopts a conformation that does not conform to the previously characterized open, closed, or intermediate states. In the ADP bound structure, the C-terminal tail and Gly-rich loop are more closed than in the open state adopted in the apo structure but are also much more open than the intermediate or closed conformations. Furthermore, ADP binds at the active site with only one magnesium ion, termed Mg2 from previous structures. These structures thus support a model where ADP release proceeds through release of the substrate and Mg1 followed by lifting of the Gly-rich loop and disengagement of the C-terminal tail. Coupling of these two structural elements with the release of the first metal ion fills in a key step in the catalytic cycle that has been missing and supports an ensemble of correlated conformational states that mediate the full catalytic cycle for a protein kinase.

PubMed: 25077557
DOI: 10.1021/bi500684c

Experimental method

X-RAY DIFFRACTION (2.9 Å)