PDBsum entry 3ku2

Transferase

PDB id: 3ku2

Contents

Protein chain

457 a.a.

Ligands

ANP

UNX ×3

Waters ×78

References listed in PDB file

Key reference

• Title: Structures of apicomplexan calcium-Dependent protein kinases reveal mechanism of activation by calcium.
• Authors: A.K.Wernimont, J.D.Artz, P.Finerty, Y.H.Lin, M.Amani, A.Allali-Hassani, G.Senisterra, M.Vedadi, W.Tempel, F.Mackenzie, I.Chau, S.Lourido, L.D.Sibley, R.Hui.
• Ref.: Nat Struct Biol, 2010, 17, 596-601.
• PubMed id: 20436473

Abstract

Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium binding triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.