View source for 4a5b


==Crystal structure of the C258S/C268S variant of Toxoplasma gondii nucleoside triphosphate diphosphohydrolase 1 (NTPDase1)==
<StructureSection load='4a5b' size='340' side='right'caption='[[4a5b]], [[Resolution|resolution]] 2.48&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4a5b]] is a 2 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=4A5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A5B 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]] 2.48&#8491;</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=4a5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a5b OCA], [https://pdbe.org/4a5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a5b RCSB], [https://www.ebi.ac.uk/pdbsum/4a5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a5b ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The intracellular parasite Toxoplasma gondii produces two nucleoside triphosphate diphosphohydrolases (NTPDase1 and -3). These tetrameric, cysteine-rich enzymes require activation by reductive cleavage of a hitherto unknown disulfide bond. Despite a 97% sequence identity both isozymes differ largely in their ability to hydrolyze ATP and ADP. Here, we present crystal structures of inactive NTPDase3 as apo form and in complex with the product AMP to resolutions of 2.0 Ang. and 2.2 Ang., respectively. We find that the enzyme is present in an open conformation that precludes productive substrate binding and catalysis. The cysteine bridge 258-268 is identified to be responsible for locking of activity. Crystal structures of constitutively active variants of NTPDase1 and -3 generated by mutation of C258-C268 show that opening of the regulatory cysteine bridge induces a pronounced contraction of the whole tetramer. This is accompanied by a 12 deg domain closure motion resulting in the correct arrangement of all active site residues. A complex structure of activated NTPDase3 with a non-hydrolyzable ATP analog and the cofactor Mg2+ to a resolution of 2.85 Ang. indicates that catalytic differences between the NTPDases are primarily dictated by differences in positioning of the adenine base caused by substitution of R492 and E493 in NTPDase1 by glycines in NTPDase3.

Structural insight into the activation mechanism of Toxoplasma gondii nucleoside triphosphate diphosphohydrolases by disulfide reduction.,Krug U, Zebisch M, Krauss M, Strater N J Biol Chem. 2011 Nov 30. PMID:22130673<ref>PMID:22130673</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Ectonucleoside triphosphate diphosphohydrolase|Ectonucleoside triphosphate diphosphohydrolase]]
*[[Nucleoside triphosphatase|Nucleoside triphosphatase]]
*[[Sandbox 30008|Sandbox 30008]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Toxoplasma gondii]]
[[Category: Krug U]]
[[Category: Strater N]]
[[Category: Zebisch M]]