4JRN

ROP18 kinase domain in complex with AMP-PNP and sucrose

Summary for 4JRN

• Entry DOI: 10.2210/pdb4jrn/pdb
• Related PRD ID: PRD_900003
• Descriptor: Rhoptry kinase family protein, beta-D-fructofuranose-(2-1)-alpha-D-glucopyranose, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: protein kinase, kinase, membrane, transferase
• Biological source: Toxoplasma gondii
• Total number of polymer chains: 1
• Total formula weight: 42403.27

Authors

Lim, D.,Gold, D.A.,Lindsay, J.,Rosowski, E.E.,Niedelman, W.,Yaffe, M.B.,Saeij, J.P.J. (deposition date: 2013-03-21, release date: 2013-10-23, Last modification date: 2024-11-27)

Primary citation

Lim, D.,Gold, D.A.,Julien, L.,Rosowski, E.E.,Niedelman, W.,Yaffe, M.B.,Saeij, J.P.
Structure of the Toxoplasma gondii ROP18 kinase domain reveals a second ligand binding pocket required for acute virulence.
J.Biol.Chem., 288:34968-34980, 2013

PubMed Abstract: At least a third of the human population is infected with the intracellular parasite Toxoplasma gondii, which contributes significantly to the disease burden in immunocompromised and neutropenic hosts and causes serious congenital complications when vertically transmitted to the fetus. Genetic analyses have identified the Toxoplasma ROP18 Ser/Thr protein kinase as a major factor mediating acute virulence in mice. ROP18 is secreted into the host cell during the invasion process, and its catalytic activity is required for the acute virulence phenotype. However, its precise molecular function and regulation are not fully understood. We have determined the crystal structure of the ROP18 kinase domain, which is inconsistent with a previously proposed autoinhibitory mechanism of regulation. Furthermore, a sucrose molecule bound to our structure identifies an additional ligand-binding pocket outside of the active site cleft. Mutational analysis confirms an important role for this pocket in virulence.

PubMed: 24129568
DOI: 10.1074/jbc.M113.523266

Experimental method

X-RAY DIFFRACTION (2.71 Å)