View source for 3uj6


==SeMet Phosphoethanolamine methyltransferase from Plasmodium falciparum in complex with SAM and PO4==
<StructureSection load='3uj6' size='340' side='right'caption='[[3uj6]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3uj6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UJ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UJ6 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]] 1.974&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=3uj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uj6 OCA], [https://pdbe.org/3uj6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uj6 RCSB], [https://www.ebi.ac.uk/pdbsum/3uj6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uj6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PMT_PLAF7 PMT_PLAF7] Catalyzes N-methylation of phosphoethanolamine, phosphomonomethylethanolamine and phosphodimethylethanolamine, the three methylation steps required to convert phosphoethanolamine to phosphocholine (PubMed:15073329, PubMed:15664981, PubMed:18178564, PubMed:18694927, PubMed:22117061). Has no ethanolamine- or phosphatidylethanolamine-N-methyltransferase activity (PubMed:15073329, PubMed:15664981). Required for gametocyte development, maturation and transmission to mosquitoes and for oocyst formation in the mosquito midgut (PubMed:24145416).<ref>PMID:15073329</ref> <ref>PMID:15664981</ref> <ref>PMID:18178564</ref> <ref>PMID:18694927</ref> <ref>PMID:22117061</ref> <ref>PMID:24145416</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In the malarial parasite Plasmodium falciparum, a multi-functional phosphoethanolamine methyltransferase (PfPMT) catalyzes the methylation of phosphoethanolamine (pEA) to phosphocholine (pCho) for membrane biogenesis. This pathway is also found in plant and nematodes, but PMT from these organisms use multiple methyltransferse domains for the AdoMet reactions. Because PfPMT is essential for normal growth and survival of Plasmodium and is not found in humans, it is an anti-parasitic target. Here we describe the 1.55 A resolution crystal structure of PfPMT in complex with S-adenosylmethionine (AdoMet) by single-wavelength anomalous dispersion phasing. In addition, 1.19-1.52 A resolution structures of PfPMT with pEA (substrate), pCho (product), sinefungin (inhibitor), and both pEA and S-adenosylhomocysteine (AdoCys) bound were determined. These structures suggest that domain rearrangements occur upon ligand binding and provide insight on active site architecture defining the AdoMet and phosphobase binding sites. Functional characterization of 27 site-directed mutants identifies critical active site residues and suggests that Tyr19 and His132 form a catalytic dyad. Kinetic analysis, isothermal titration calorimetry, and protein crystallography of the Y19F and H132A mutants suggest a reaction mechanism for the PMT. Not only are Tyr19 and His132 required for phosphobase methylation, but they also form a 'catalytic' latch that locks ligands in the active site and orders the site for catalysis. This study provides the first insight on this anti-parasitic target enzyme essential for survival of the malaria parasite; however, further studies of the multi-domain PMT from plants and nematodes are needed to understand the evolutionary division of metabolic function in the phosphobase pathway of these organisms.

Structure and Reaction Mechanism of Phosphoethanolamine Methyltransferase from the Malaria Parasite Plasmodium falciparum: An Anti-Parasitic Drug Target.,Lee SG, Kim Y, Alpert TD, Nagata A, Jez JM J Biol Chem. 2011 Nov 23. PMID:22117061<ref>PMID:22117061</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3uj6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Alpert TD]]
[[Category: Jez JM]]
[[Category: Kim Y]]
[[Category: Lee SG]]
[[Category: Nagata A]]