Download MendeleyThe Structure of Msk1 Reveals a Novel Autoinhibitory Conformation for a Dual Kinase Protein
Smith, K.J., Carter, P.S., Bridges, A., Horrocks, P., Lewis, C., Pettman, G., Clarke, A., Brown, M., Hughes, J., Wilkinson, M., Bax, B., Reith, A.(2004) Structure 12: 1066
- PubMed: 15274926
- DOI: https://doi.org/10.1016/j.str.2004.02.040
- Primary Citation of Related Structures:
1VZO - PubMed Abstract:
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.
Organizational Affiliation:
Discovery Research, GlaxoSmithKline, Third Ave, Harlow, Essex, CM19 5AW, United Kingdom. [email protected]
