1j3h

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spinqualitylabelsall models 1j3h, resolution 2.9Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of apoenzyme cAMP-dependent protein kinase catalytic subunit

Overview

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.

About this Structure

1J3H is a Single protein structure of sequence from Mus musculus with MPD as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.

Reference

Dynamic features of cAMP-dependent protein kinase revealed by apoenzyme crystal structure., Akamine P, Madhusudan, Wu J, Xuong NH, Ten Eyck LF, Taylor SS, J Mol Biol. 2003 Mar 14;327(1):159-71. PMID:12614615

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