View source for 4wim


==Crystal Structure of the GMP Synthetase from Plasmodium falciparum==
<StructureSection load='4wim' size='340' side='right'caption='[[4wim]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wim]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WIM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WIM 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]] 3.6&#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=4wim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wim OCA], [https://pdbe.org/4wim PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wim RCSB], [https://www.ebi.ac.uk/pdbsum/4wim PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wim ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8IJR9_PLAF7 Q8IJR9_PLAF7] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
GMP synthetase (GMPS), a key enzyme in the purine biosynthetic pathway performs catalysis through a coordinated process across two catalytic pockets for which the mechanism remains unclear. Crystal structures of Plasmodium falciparum GMPS in conjunction with mutational and enzyme kinetic studies reported here provide evidence that an 85 degrees rotation of the GATase domain is required for ammonia channelling and thus for the catalytic activity of this two-domain enzyme. We suggest that conformational changes in helix 371-375 holding catalytic residues and in loop 376-401 along the rotation trajectory trigger the different steps of catalysis, and establish the central role of Glu374 in allostery and inter-domain crosstalk. These studies reveal the mechanism of domain rotation and inter-domain communication, providing a molecular framework for the function of all single polypeptide GMPSs and form a solid basis for rational drug design targeting this therapeutically important enzyme.

Active site coupling in Plasmodium falciparum GMP synthetase is triggered by domain rotation.,Ballut L, Violot S, Shivakumaraswamy S, Thota LP, Sathya M, Kunala J, Dijkstra BW, Terreux R, Haser R, Balaram H, Aghajari N Nat Commun. 2015 Nov 23;6:8930. doi: 10.1038/ncomms9930. PMID:26592566<ref>PMID:26592566</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4wim" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Aghajari N]]
[[Category: Ballut L]]
[[Category: Haser R]]
[[Category: Violot S]]