2biy

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spinqualitylabelsall models 2biy, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURE OF PDK1-S241A MUTANT KINASE DOMAIN

Overview

3-Phosphoinositide-dependent protein kinase-1 (PDK1) phosphorylates the, T-loop of several AGC (cAMP-dependent, cGMP-dependent, protein kinase C), family protein kinases, resulting in their activation. Previous structural, studies have revealed that the alpha C-helix, located in the small lobe of, the kinase domain of PDK1, is a key regulatory element, as it links a, substrate interacting site termed the hydrophobic motif (HM) pocket with, the phosphorylated Ser-241 in the T-loop. In this study we have, demonstrated by mutational analysis that interactions between the, phosphorylated Ser-241 and the alpha C-helix are not required for PDK1, activity or substrate binding through the HM-pocket but are necessary for, PDK1 to be activated or stabilized by a peptide that binds to this site., The structure of an inactive T-loop mutant of PDK1, in which Ser-241 is, changed to Ala, was also determined. This structure, together with surface, plasmon resonance binding studies, demonstrates that the, PDK1(S241A)-inactive mutant possesses an intact HM-pocket as well as an, ordered alpha C-helix. These findings reveal that the integrity of the, alpha C-helix and HM-pocket in PDK1 is not regulated by T-loop, phosphorylation.

About this Structure

2BIY is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Role of T-loop phosphorylation in PDK1 activation, stability, and substrate binding., Komander D, Kular G, Deak M, Alessi DR, van Aalten DM, J Biol Chem. 2005 May 13;280(19):18797-802. Epub 2005 Mar 1. PMID:15741170

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