Details

Autor(en) / Beteiligte

• Smith, Kathrine J
• Carter, Paul S
• Bridges, Angela
• Horrocks, Pete
• Lewis, Ceri
• Pettman, Gary
• Clarke, Andrew
• Brown, Murray
• Hughes, Jane
• Wilkinson, Marc
• Bax, Benjamin
• Reith, Alastair

Titel

The Structure of MSK1 Reveals a Novel Autoinhibitory Conformation for a Dual Kinase Protein

Ist Teil von

• Structure (London), 2004-06, Vol.12 (6), p.1067-1077

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2004

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 Å 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 β sheet on the N lobe of the kinase domain. The three β strands come from residues at the N terminus of the kinase domain, what would be the αB helix in the active conformation, and the activation loop. The new three-stranded β sheet occupies a position equivalent to the N terminus of the αC helix in active protein kinases.