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< | ==Crystal structure of a rhoptry kinase from toxoplasma gondii== | ||
<StructureSection load='3dzo' size='340' side='right'caption='[[3dzo]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3dzo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DZO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DZO FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dzo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dzo OCA], [https://pdbe.org/3dzo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dzo RCSB], [https://www.ebi.ac.uk/pdbsum/3dzo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dzo ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q06AK3_TOXGO Q06AK3_TOXGO] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dz/3dzo_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3dzo ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii.,Qiu W, Wernimont A, Tang K, Taylor S, Lunin V, Schapira M, Fentress S, Hui R, Sibley LD EMBO J. 2009 Apr 8;28(7):969-79. Epub 2009 Feb 5. PMID:19197235<ref>PMID:19197235</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
== | </div> | ||
<div class="pdbe-citations 3dzo" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Toxoplasma gondii]] | [[Category: Toxoplasma gondii]] | ||
[[Category: Ali | [[Category: Ali A]] | ||
[[Category: Arrowsmith | [[Category: Arrowsmith CH]] | ||
[[Category: Bochkarev | [[Category: Bochkarev A]] | ||
[[Category: Bountra | [[Category: Bountra C]] | ||
[[Category: Edwards | [[Category: Edwards AM]] | ||
[[Category: Hui | [[Category: Hui R]] | ||
[[Category: Kozieradzki | [[Category: Kozieradzki I]] | ||
[[Category: Lam | [[Category: Lam A]] | ||
[[Category: Lin | [[Category: Lin YH]] | ||
[[Category: Ni | [[Category: Ni S]] | ||
[[Category: Qiu | [[Category: Qiu W]] | ||
[[Category: Ravichandran | [[Category: Ravichandran M]] | ||
[[Category: Schapira M]] | |||
[[Category: Schapira | [[Category: Sibley D]] | ||
[[Category: Sibley | [[Category: Vedadi M]] | ||
[[Category: Vedadi | [[Category: Wasney G]] | ||
[[Category: Wasney | [[Category: Wernimont AK]] | ||
[[Category: Wernimont | [[Category: Wilkstrom M]] | ||
[[Category: Wilkstrom | |||
Latest revision as of 15:55, 30 August 2023
Crystal structure of a rhoptry kinase from toxoplasma gondiiCrystal structure of a rhoptry kinase from toxoplasma gondii
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSerine/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. Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii.,Qiu W, Wernimont A, Tang K, Taylor S, Lunin V, Schapira M, Fentress S, Hui R, Sibley LD EMBO J. 2009 Apr 8;28(7):969-79. Epub 2009 Feb 5. PMID:19197235[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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