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5c1s

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'''Unreleased structure'''
 
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The entry 5c1s is ON HOLD until Paper Publication
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==Crystal structure of the GDP-bound fast hydrolyzing mutant (V71A/K73Q) of EhRabX3 from Entamoeba histolytica==
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<StructureSection load='5c1s' size='340' side='right' caption='[[5c1s]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5c1s]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C1S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C1S FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5c1t|5c1t]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5c1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c1s OCA], [http://pdbe.org/5c1s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c1s RCSB], [http://www.ebi.ac.uk/pdbsum/5c1s PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The enteric protozoan parasite, Entamoeba histolytica, is the causative agent of amoebic dysentery, liver abscess and colitis in human. Vesicular trafficking plays a key role in the survival and virulence of the protozoan and is regulated by various Rab GTPases. EhRabX3 is a catalytically inefficient amoebic Rab protein, which is unique among the eukaryotic Ras superfamily by virtue of its tandem domain organization. Here, we report the crystal structures of GDP-bound fast hydrolyzing mutant (V71A/K73Q) and GTP-bound wild type EhRabX3 at 3.1 and 2.8A resolutions, respectively. Though both G-domains possess "phosphate binding loop containing nucleoside triphosphate hydrolases fold", only the N-terminal domain binds to guanine nucleotide. The relative orientation of the N-terminal domain and C-terminal domain is stabilized by numerous inter-domain interactions. Compared to other Ras superfamily members, both the GTPase domains displayed large deviation in switch II perhaps due to non-conservative substitutions in this region. As a result, entire switch II is restructured and moved away from the nucleotide binding pocket, providing a rationale for the diminished GTPase activity of EhRabX3. The N-terminal GTPase domain possesses unusually large number of cysteine residues. X-ray crystal structure of the fast hydrolyzing mutant of EhRabX3 revealed that C39 and C163 formed an intra-molecular disulfide bond. Subsequent mutational and biochemical studies suggest that C39 and C163 are critical for maintaining the structural integrity and function of EhRabX3. Structure-guided functional investigation of cysteine mutants could provide the physiological implications of the disulfide bond and could allow us to design potential inhibitors for the better treatment of intestinal amebiasis.
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Authors: Srivastava, V.K., Chandra, M., Datta, S.
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Crystal Structure Analysis of Wild Type and Fast Hydrolyzing Mutant of EhRabX3, a Tandem Ras Superfamily GTPase from Entamoeba histolytica.,Srivastava VK, Chandra M, Saito-Nakano Y, Nozaki T, Datta S J Mol Biol. 2016 Jan 16;428(1):41-51. doi: 10.1016/j.jmb.2015.11.003. Epub 2015, Nov 10. PMID:26555751<ref>PMID:26555751</ref>
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Description: Crystal structure of the GDP-bound fast hydrolyzing mutant (V71A/K73Q) of EhRabX3 from Entamoeba histolytica
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Datta, S]]
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<div class="pdbe-citations 5c1s" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Chandra, M]]
[[Category: Chandra, M]]
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[[Category: Srivastava, V.K]]
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[[Category: Datta, S]]
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[[Category: Srivastava, V K]]
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[[Category: Hydrolase]]
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[[Category: P-loop containing nucleotide triphosphate hydrolases fold]]
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[[Category: Tandem gtpase]]

Revision as of 12:00, 13 May 2016

Crystal structure of the GDP-bound fast hydrolyzing mutant (V71A/K73Q) of EhRabX3 from Entamoeba histolytica

5c1s, resolution 3.10Å

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