3KHE

Crystal structure of the calcium-loaded calmodulin-like domain of the CDPK, 541.m00134 from toxoplasma gondii

3KHE の概要

• エントリーDOI: 10.2210/pdb3khe/pdb
• 分子名称: Calmodulin-like domain protein kinase isoform 3, CALCIUM ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: calcium dependent kinase, structural genomics, structural genomics consortium, sgc, atp-binding, kinase, nucleotide-binding, serine/threonine-protein kinase, metal binding protein
• 由来する生物種: Toxoplasma gondii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44354.71

構造登録者

Wernimont, A.K.,Hutchinson, A.,Artz, J.D.,Mackenzie, F.,Cossar, D.,Kozieradzki, I.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Weigelt, J.,Bochkarev, A.,Hui, R.,Qiu, W.,Amani, M.,Structural Genomics Consortium (SGC) (登録日: 2009-10-30, 公開日: 2010-01-19, 最終更新日: 2024-02-21)

主引用文献

Wernimont, A.K.,Amani, M.,Qiu, W.,Pizarro, J.C.,Artz, J.D.,Lin, Y.H.,Lew, J.,Hutchinson, A.,Hui, R.
Structures of parasitic CDPK domains point to a common mechanism of activation.
Proteins, 79:803-820, 2011

PubMed Abstract: We recently determined the first structures of inactivated and calcium-activated calcium-dependent protein kinases (CDPKs) from Apicomplexa. Calcium binding triggered a large conformational change that constituted a new mechanism in calcium signaling and a novel EF-hand fold (CAD, for CDPK activation domain). Thus we set out to determine if this mechanism was universal to all CDPKs. We solved additional CDPK structures, including one from the species Plasmodium. We highlight the similarities in sequence and structure across apicomplexan and plant CDPKs, and strengthen our observations that this novel mechanism could be universal to canonical CDPKs. Our new structures demonstrate more detailed steps in the mechanism of calcium activation and possible key players in regulation. Residues involved in making the largest conformational change are the most conserved across Apicomplexa, leading us to propose that the mechanism is indeed conserved. CpCDPK3_CAD and PfCDPK_CAD were captured at a possible intermediate conformation, lending insight into the order of activation steps. PfCDPK3_CAD adopts an activated fold, despite having an inactive EF-hand sequence in the N-terminal lobe. We propose that for most apicomplexan CDPKs, the mode of activation will be similar to that seen in our structures, while specific regulation of the inactive and active forms will require further investigation.

PubMed: 21287613
DOI: 10.1002/prot.22919

実験手法

X-RAY DIFFRACTION (1.95 Å)