1J3H

Crystal structure of apoenzyme cAMP-dependent protein kinase catalytic subunit

Summary for 1J3H

• Entry DOI: 10.2210/pdb1j3h/pdb
• Related: 1ATP 1BKX 1CMK 1CTP 1L3R
• Descriptor: cAMP-dependent protein kinase, alpha-catalytic subunit, (4S)-2-METHYL-2,4-PENTANEDIOL (2 entities in total)
• Functional Keywords: apoenzyme, camp-dependent protein kinase, catalytic subunit, open conformation, preformed active site, transferase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm (By similarity): P05132
• Total number of polymer chains: 2
• Total formula weight: 81703.22

Authors

Akamine, P.,Madhusudan,Wu, J.,Xuong, N.H.,Ten Eyck, L.F.,Taylor, S.S. (deposition date: 2003-01-31, release date: 2003-03-04, Last modification date: 2024-10-30)

Primary citation

Akamine, P.,Madhusudan,Wu, J.,Xuong, N.-H.,Ten Eyck, L.F.,Taylor, S.S.
Dynamic Features of cAMP-dependent Protein Kinase Revealed by Apoenzyme Crystal Structure
J.Mol.Biol., 327:159-171, 2003

PubMed Abstract: To better understand the mechanism of ligand binding and ligand-induced conformational change, the crystal structure of apoenzyme catalytic (C) subunit of adenosine-3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) was solved. The apoenzyme structure (Apo) provides a snapshot of the enzyme in the first step of the catalytic cycle, and in this unliganded form the PKA C subunit adopts an open conformation. A hydrophobic junction is formed by residues from the small and large lobes that come into close contact. This "greasy" patch may lubricate the shearing motion associated with domain rotation, and the opening and closing of the active-site cleft. Although Apo appears to be quite dynamic, many important residues for MgATP binding and phosphoryl transfer in the active site are preformed. Residues around the adenine ring of ATP and residues involved in phosphoryl transfer from the large lobe are mostly preformed, whereas residues involved in ribose binding and in the Gly-rich loop are not. Prior to ligand binding, Lys72 and the C-terminal tail, two important ATP-binding elements are also disordered. The surface created in the active site is contoured to bind ATP, but not GTP, and appears to be held in place by a stable hydrophobic core, which includes helices C, E, and F, and beta strand 6. This core seems to provide a network for communicating from the active site, where nucleotide binds, to the peripheral peptide-binding F-to-G helix loop, exemplified by Phe239. Two potential lines of communication are the D helix and the F helix. The conserved Trp222-Phe238 network, which lies adjacent to the F-to-G helix loop, suggests that this network would exist in other protein kinases and may be a conserved means of communicating ATP binding from the active site to the distal peptide-binding ledge.

PubMed: 12614615
DOI: 10.1016/S0022-2836(02)01446-8

Experimental method

X-RAY DIFFRACTION (2.9 Å)