3DZO

Crystal structure of a rhoptry kinase from toxoplasma gondii

3DZO の概要

• エントリーDOI: 10.2210/pdb3dzo/pdb
• 関連するPDBエントリー: 3BYV
• 分子名称: Rhoptry kinase domain, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: rhoptry kinase, toxoplasma, parasitic disease, transferase, structural genomics, structural genomics consortium, sgc
• 由来する生物種: Toxoplasma gondii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46986.46

構造登録者

Wernimont, A.K.,Lam, A.,Ali, A.,Lin, Y.H.,Ni, S.,Ravichandran, M.,Wasney, G.,Vedadi, M.,Kozieradzki, I.,Schapira, M.,Bochkarev, A.,Wilkstrom, M.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Sibley, D.,Hui, R.,Qiu, W.,Structural Genomics Consortium (SGC) (登録日: 2008-07-30, 公開日: 2008-09-16, 最終更新日: 2024-11-13)

主引用文献

Qiu, W.,Wernimont, A.,Tang, K.,Taylor, S.,Lunin, V.,Schapira, M.,Fentress, S.,Hui, R.,Sibley, L.D.
Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii.
Embo J., 28:969-979, 2009

PubMed Abstract: Serine/threonine kinases secreted from rhoptry organelles constitute important virulence factors of Toxoplasma gondii. Rhoptry kinases are highly divergent and their structures and regulatory mechanism are hitherto unknown. Here, we report the X-ray crystal structures of two related pseudokinases named ROP2 and ROP8, which differ primarily in their substrate-binding site. ROP kinases contain a typical bilobate kinase fold and a novel N-terminal extension that both stabilizes the N-lobe and provides a unique means of regulation. Although ROP2 and ROP8 were catalytically inactive, they provided a template for homology modelling of the active kinase ROP18, a major virulence determinant of T. gondii. Autophosphorylation of key residues in the N-terminal extension resulted in ROP18 activation, which in turn phosphorylated ROP2 and ROP8. Mutagenesis and mass spectrometry experiments revealed that ROP18 was maximally activated when this phosphorylated N-terminus relieved autoinhibition resulting from extension of aliphatic side chains into the ATP-binding pocket. This novel means of regulation governs ROP kinases implicated in parasite virulence.

PubMed: 19197235
DOI: 10.1038/emboj.2009.24

実験手法

X-RAY DIFFRACTION (1.8 Å)