3KN5

Crystal structure of the C-terminal kinase domain of msk1 in complex with AMP-PNP

Summary for 3KN5

• Entry DOI: 10.2210/pdb3kn5/pdb
• Related: 3KN6
• Descriptor: Ribosomal protein S6 kinase alpha-5, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (3 entities in total)
• Functional Keywords: kinase, amp-pnp, msk1, msk, atp-binding, metal-binding, nucleotide-binding, serine/threonine-protein kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O75582
• Total number of polymer chains: 2
• Total formula weight: 75023.39

Authors

D'Angelo, I.,Malakhova, M.,Dong, Z. (deposition date: 2009-11-12, release date: 2010-04-21, Last modification date: 2024-11-27)

Primary citation

Malakhova, M.,D'Angelo, I.,Kim, H.G.,Kurinov, I.,Bode, A.M.,Dong, Z.
The crystal structure of the active form of the C-terminal kinase domain of mitogen- and stress-activated protein kinase 1.
J.Mol.Biol., 399:41-52, 2010

PubMed Abstract: Mitogen- and stress-activated protein kinase 1 (MSK1) is a growth-factor-stimulated serine/threonine kinase that is involved in gene transcription regulation and proinflammatory cytokine stimulation. MSK1 is a dual kinase possessing two nonidentical protein kinase domains in one polypeptide. We present the active conformation of the crystal structures of its C-terminal kinase domain in apo form and in complex with a nonhydrolyzable ATP analogue at 2.0 A and 2.5 A resolutions, respectively. Structural analysis revealed substantial differences in the contacts formed by the C-terminal helix, which is responsible for the inactivity of other autoinhibited kinases. In the C-terminal kinase domain of MSK1, the C-terminal alphaL-helix is located in the surface groove, but forms no hydrogen bonds with the substrate-binding loop or nearby helices, and does not interfere with the protein's autophosphorylation activity. Mutational analysis confirmed that the alphaL-helix is inherently nonautoinhibitory. Overexpression of the single C-terminal kinase domain in JB6 cells resulted in tumor-promoter-induced neoplastic transformation in a manner similar to that induced by the full-length MSK1 protein. The overall results suggest that the C-terminal kinase domain of MSK1 is regulated by a novel alphaL-helix-independent mechanism, suggesting that a diverse mechanism of autoinhibition and activation might be adopted by members of a closely related protein kinase family.

PubMed: 20382163
DOI: 10.1016/j.jmb.2010.03.064

Experimental method

X-RAY DIFFRACTION (2.4 Å)