1zrz

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spinqualitylabelsall models 1zrz, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of the Catalytic Domain of Atypical Protein Kinase C-iota

Overview

Atypical protein kinases C (aPKCs) play critical roles in signaling, pathways that control cell growth, differentiation and survival., Therefore, they constitute attractive targets for the development of novel, therapeutics against cancer. The crystal structure of the catalytic domain, of atypical PKCiota in complex with the bis(indolyl)maleimide inhibitor, BIM1 has been determined at 3.0A resolution within the frame of the, European Structural Proteomics Project SPINE. The overall structure, exhibits the classical bilobal kinase fold and is in its fully activated, form. Both phosphorylation sites (Thr403 in the activation loop, and, Thr555 in the turn motif) are well defined in the structure and form, intramolecular ionic contacts that make an important contribution in, stabilizing the active conformation of the catalytic subunit. The, phosphorylation site in the hydrophobic motif of atypical PKCs is replaced, by the phosphorylation mimic glutamate and this is also clearly seen in, the structure of PKCiota (residue 574). This structure determination for, the first time provides the architecture of the turn motif phosphorylation, site, which is characteristic for PKCs and PKB/AKT, and is completely, different from that in PKA. The bound BIM1 inhibitor blocks the, ATP-binding site and puts the kinase domain into an intermediate open, conformation. The PKCiota-BIM1 complex is the first kinase domain crystal, structure of any atypical PKC and constitutes the basis for rational drug, design for selective PKCiota inhibitors.

About this Structure

1ZRZ is a Single protein structure of sequence from Homo sapiens with BI1 as ligand. Full crystallographic information is available from OCA.

Reference

Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif., Messerschmidt A, Macieira S, Velarde M, Badeker M, Benda C, Jestel A, Brandstetter H, Neuefeind T, Blaesse M, J Mol Biol. 2005 Sep 30;352(4):918-31. PMID:16125198

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