1YRP

Catalytic domain of human ZIP kinase phosphorylated at Thr265

Summary for 1YRP

• Entry DOI: 10.2210/pdb1yrp/pdb
• Descriptor: Death-associated protein kinase 3, 2,3-DIHYDROXY-1,4-DITHIOBUTANE (2 entities in total)
• Functional Keywords: kinase fold, phosphothreonine, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus . Isoform 1: Nucleus . Isoform 2: Nucleus : O43293
• Total number of polymer chains: 2
• Total formula weight: 64273.05

Authors

Kursula, P.,Vahokoski, J.,Wilmanns, M. (deposition date: 2005-02-04, release date: 2006-06-20, Last modification date: 2024-10-23)

Primary citation

Simon, B.,Huart, A.S.,Temmerman, K.,Vahokoski, J.,Mertens, H.D.,Komadina, D.,Hoffmann, J.E.,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, 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 (3.1 Å)