1vzo
From Proteopedia
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==Overview== | ==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. | 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. | ||
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| + | ==Disease== | ||
| + | Known disease associated with this structure: Spondyloepiphyseal dysplasia, Kimberley type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155760 155760]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:45:14 2007'' |
Revision as of 17:38, 12 November 2007
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THE STRUCTURE OF THE N-TERMINAL KINASE DOMAIN OF MSK1 REVEALS A NOVEL AUTOINHIBITORY CONFORMATION FOR A DUAL KINASE PROTEIN
Contents |
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 SO4 and BME as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Structure known Active Site: BME. 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 Mon Nov 12 19:45:14 2007
Categories: Homo sapiens | Single protein | Transferred entry: 2.7.11.1 | Bax, B. | Bridges, A. | Brown, M. | Carter, P.S. | Clarke, A. | Horrocks, P. | Hughes, J. | Lewis, C. | Pettman, G. | Reith, A. | Smith, K.J. | Wilkinson, M. | BME | SO4 | Phosphorylation | Protein kinase | Serine/threonine protein kinase | Transferase
