1CMK

CRYSTAL STRUCTURES OF THE MYRISTYLATED CATALYTIC SUBUNIT OF CAMP-DEPENDENT PROTEIN KINASE REVEAL OPEN AND CLOSED CONFORMATIONS

Summary for 1CMK

• Entry DOI: 10.2210/pdb1cmk/pdb
• Descriptor: cAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT, cAMP-dependent protein kinase inhibitor, alpha form, MYRISTIC ACID, ... (4 entities in total)
• Functional Keywords: phosphotransferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Sus scrofa (pig); More
• Cellular location: Cytoplasm: P00517
• Total number of polymer chains: 2
• Total formula weight: 43640.29

Authors

Zheng, J.,Knighton, D.R.,Xuong, N.-H.,Taylor, S.S.,Sowadski, J.M.,Ten Eyck, L.F. (deposition date: 1993-11-18, release date: 1994-05-31, Last modification date: 2024-12-25)

Primary citation

Zheng, J.,Knighton, D.R.,Xuong, N.H.,Taylor, S.S.,Sowadski, J.M.,Ten Eyck, L.F.
Crystal structures of the myristylated catalytic subunit of cAMP-dependent protein kinase reveal open and closed conformations.
Protein Sci., 2:1559-1573, 1993

PubMed Abstract: Three crystal structures, representing two distinct conformational states, of the mammalian catalytic subunit of cAMP-dependent protein kinase were solved using molecular replacement methods starting from the refined structure of the recombinant catalytic subunit ternary complex (Zheng, J., et al., 1993a, Biochemistry 32, 2154-2161). These structures correspond to the free apoenzyme, a binary complex with an iodinated inhibitor peptide, and a ternary complex with both ATP and the unmodified inhibitor peptide. The apoenzyme and the binary complex crystallized in an open conformation, whereas the ternary complex crystallized in a closed conformation similar to the ternary complex of the recombinant enzyme. The model of the binary complex, refined at 2.9 A resolution, shows the conformational changes associated with the open conformation. These can be described by a rotation of the small lobe and a displacement of the C-terminal 30 residues. This rotation of the small lobe alters the cleft interface in the active-site region surrounding the glycine-rich loop and Thr 197, a critical phosphorylation site. In addition to the conformational changes, the myristylation site, absent in the recombinant enzyme, was clearly defined in the binary complex. The myristic acid binds in a deep hydrophobic pocket formed by four segments of the protein that are widely dispersed in the linear sequence. The N-terminal 40 residues that lie outside the conserved catalytic core are anchored by the N-terminal myristylate plus an amphipathic helix that spans both lobes and is capped by Trp 30. Both posttranslational modifications, phosphorylation and myristylation, contribute directly to the stable structure of this enzyme.

PubMed: 8251932

Experimental method

X-RAY DIFFRACTION (2.9 Å)