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1vzo

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==Overview==
==Overview==
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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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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==
==Disease==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Transferred entry: 2.7.11.1]]
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[[Category: Transferred entry: 2 7.11 1]]
[[Category: Bax, B.]]
[[Category: Bax, B.]]
[[Category: Bridges, A.]]
[[Category: Bridges, A.]]
[[Category: Brown, M.]]
[[Category: Brown, M.]]
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[[Category: Carter, P.S.]]
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[[Category: Carter, P S.]]
[[Category: Clarke, A.]]
[[Category: Clarke, A.]]
[[Category: Horrocks, P.]]
[[Category: Horrocks, P.]]
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[[Category: Pettman, G.]]
[[Category: Pettman, G.]]
[[Category: Reith, A.]]
[[Category: Reith, A.]]
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[[Category: Smith, K.J.]]
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[[Category: Smith, K J.]]
[[Category: Wilkinson, M.]]
[[Category: Wilkinson, M.]]
[[Category: BME]]
[[Category: BME]]
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[[Category: transferase]]
[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:17:33 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:39:01 2008''

Revision as of 13:39, 21 February 2008


1vzo, resolution 1.80Å

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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 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

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