1CDK

CAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT (E.C.2.7.1.37) (PROTEIN KINASE A) COMPLEXED WITH PROTEIN KINASE INHIBITOR PEPTIDE FRAGMENT 5-24 (PKI(5-24) ISOELECTRIC VARIANT CA) AND MN2+ ADENYLYL IMIDODIPHOSPHATE (MNAMP-PNP) AT PH 5.6 AND 7C AND 4C

Summary for 1CDK

• Entry DOI: 10.2210/pdb1cdk/pdb
• Descriptor: CAMP-DEPENDENT PROTEIN KINASE, PROTEIN KINASE INHIBITOR, MANGANESE (II) ION, ... (6 entities in total)
• Functional Keywords: complex (transferase-inhibitor), transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Sus scrofa (pig); More
• Cellular location: Cytoplasm: P00517
• Total number of polymer chains: 4
• Total formula weight: 87392.52

Authors

Bossemeyer, D.,Engh, R.A.,Kinzel, V.,Ponstingl, H.,Huber, R. (deposition date: 1994-07-04, release date: 1995-10-15, Last modification date: 2024-10-09)

Primary citation

Bossemeyer, D.,Engh, R.A.,Kinzel, V.,Ponstingl, H.,Huber, R.
Phosphotransferase and substrate binding mechanism of the cAMP-dependent protein kinase catalytic subunit from porcine heart as deduced from the 2.0 A structure of the complex with Mn2+ adenylyl imidodiphosphate and inhibitor peptide PKI(5-24).
EMBO J., 12:849-859, 1993

PubMed Abstract: The crystal structure of the porcine heart catalytic subunit of cAMP-dependent protein kinase in a ternary complex with the MgATP analogue MnAMP-PNP and a pseudosubstrate inhibitor peptide, PKI(5-24), has been solved at 2.0 A resolution from monoclinic crystals of the catalytic subunit isoform CA. The refinement is presently at an R factor of 0.194 and the active site of the molecule is well defined. The glycine-rich phosphate anchor of the nucleotide binding fold motif of the protein kinase is a beta ribbon acting as a flap with conformational flexibility over the triphosphate group. The glycines seem to be conserved to avoid steric clash with ATP. The known synergistic effects of substrate binding can be explained by hydrogen bonds present only in the ternary complex. Implications for the kinetic scheme of binding order are discussed. The structure is assumed to represent a phosphotransfer competent conformation. The invariant conserved residue Asp166 is proposed to be the catalytic base and Lys168 to stabilize the transition state. In some tyrosine kinases Lys168 is functionally replaced by an Arg displaced by two residues in the primary sequence, suggesting invariance in three-dimensional space. The structure supports an in-line transfer with a pentacoordinate transition state at the phosphorus with very few nuclear movements.

PubMed: 8384554

Experimental method

X-RAY DIFFRACTION (2 Å)