1vzo

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1vzo, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

THE STRUCTURE OF THE N-TERMINAL KINASE DOMAIN OF MSK1 REVEALS A NOVEL AUTOINHIBITORY CONFORMATION FOR A DUAL KINASE PROTEIN

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Mitogen and stress-activated kinase-1 (MSK1) is a serine/threonine protein kinase that is activated by either p38 or p42ERK MAPKs in response to stress or mitogenic extracellular stimuli. MSK1 belongs to a family of protein kinases that contain two distinct kinase domains in one polypeptide chain. We report the 1.8 A crystal structure of the N-terminal kinase domain of MSK1. The crystal structure reveals a unique inactive conformation with the ATP binding site blocked by the nucleotide binding loop. This inactive conformation is stabilized by the formation of a new three-stranded beta sheet on the N lobe of the kinase domain. The three beta strands come from residues at the N terminus of the kinase domain, what would be the alphaB helix in the active conformation, and the activation loop. The new three-stranded beta sheet occupies a position equivalent to the N terminus of the alphaC helix in active protein kinases.

Disease

Known disease associated with this structure: Spondyloepiphyseal dysplasia, Kimberley type OMIM:[155760]

About this Structure

1VZO 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

The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein., Smith KJ, Carter PS, Bridges A, Horrocks P, Lewis C, Pettman G, Clarke A, Brown M, Hughes J, Wilkinson M, Bax B, Reith A, Structure. 2004 Jun;12(6):1067-77. PMID:15274926

Page seeded by OCA on Thu Feb 21 15:39:01 2008