1VZO

The structure of the N-terminal kinase domain of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein

Summary for 1VZO

• Entry DOI: 10.2210/pdb1vzo/pdb
• Descriptor: RIBOSOMAL PROTEIN S6 KINASE ALPHA 5, BETA-MERCAPTOETHANOL, SULFATE ION, ... (4 entities in total)
• Functional Keywords: protein kinase, transferase, phosphorylation, serine/threonine protein kinase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus: O75582
• Total number of polymer chains: 1
• Total formula weight: 40088.57

Authors

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. (deposition date: 2004-05-21, release date: 2004-06-11, Last modification date: 2023-12-13)

Primary citation

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.
The Structure of Msk1 Reveals a Novel Autoinhibitory Conformation for a Dual Kinase Protein
Structure, 12:1066-, 2004

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.

PubMed: 15274926
DOI: 10.1016/J.STR.2004.02.040

Experimental method

X-RAY DIFFRACTION (1.8 Å)