2XZS

Death associated protein kinase 1 residues 1-312

Summary for 2XZS

• Entry DOI: 10.2210/pdb2xzs/pdb
• Related: 1IG1 1JKK 1JKL 1JKS 1JKT 1P4F 2W4J 2W4K 2X0G 2XUU 2Y0A 2Y4P 2Y4V 2YAK 3ZXT
• Descriptor: DEATH ASSOCIATED KINASE 1, MAGNESIUM ION (3 entities in total)
• Functional Keywords: transferase, calmodulin, esprit
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Isoform 1: Cytoplasm. Isoform 2: Cytoplasm: P53355
• Total number of polymer chains: 2
• Total formula weight: 71834.82

Authors

Yumerefendi, H.,Mas, P.J.,Dordevic, N.,McCarthy, A.A.,Hart, D.J. (deposition date: 2010-11-29, release date: 2011-12-07, Last modification date: 2023-12-20)

Primary citation

Simon, B.,Huart, A.,Temmerman, K.,Vahokoski, J.,Mertens, H.D.T.,Komadina, D.,Hoffmann, J.,Yumerefendi, H.,Svergun, D.I.,Kursula, P.,Schultz, C.,Mccarthy, A.A.,Hart, D.J.,Wilmanns, M.
Death-Associated Protein Kinase Activity is Regulated by Coupled Calcium/Calmodulin Binding to Two Distinct Sites.
Structure, 24:851-, 2016

PubMed Abstract: The regulation of many protein kinases by binding to calcium/calmodulin connects two principal mechanisms in signaling processes: protein phosphorylation and responses to dose- and time-dependent calcium signals. We used the calcium/calmodulin-dependent members of the death-associated protein kinase (DAPK) family to investigate the role of a basic DAPK signature loop near the kinase active site. In DAPK2, this loop comprises a novel dimerization-regulated calcium/calmodulin-binding site, in addition to a well-established calcium/calmodulin site in the C-terminal autoregulatory domain. Unexpectedly, impairment of the basic loop interaction site completely abolishes calcium/calmodulin binding and DAPK2 activity is reduced to a residual level, indicative of coupled binding to the two sites. This contrasts with the generally accepted view that kinase calcium/calmodulin interactions are autonomous of the kinase catalytic domain. Our data establish an intricate model of multi-step kinase activation and expand our understanding of how calcium binding connects with other mechanisms involved in kinase activity regulation.

PubMed: 27133022
DOI: 10.1016/J.STR.2016.03.020

Experimental method

X-RAY DIFFRACTION (2 Å)