3ujb: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3ujb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UJB FirstGlance]. <br> | <table><tr><td colspan='2'>[[3ujb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UJB FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OPE:PHOSPHORIC+ACID+MONO-(2-AMINO-ETHYL)+ESTER'>OPE</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OPE:PHOSPHORIC+ACID+MONO-(2-AMINO-ETHYL)+ESTER'>OPE</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3uj6|3uj6]], [[3uj7|3uj7]], [[3uj8|3uj8]], [[3uj9|3uj9]], [[3uja|3uja]], [[3ujc|3ujc]], [[3ujd|3ujd]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3uj6|3uj6]], [[3uj7|3uj7]], [[3uj8|3uj8]], [[3uj9|3uj9]], [[3uja|3uja]], [[3ujc|3ujc]], [[3ujd|3ujd]]</td></tr> | ||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PMT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 Plasmodium falciparum])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PMT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 Plasmodium falciparum])</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ujb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ujb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ujb RCSB], [http://www.ebi.ac.uk/pdbsum/3ujb PDBsum]</span></td></tr> | <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=3ujb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ujb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ujb RCSB], [http://www.ebi.ac.uk/pdbsum/3ujb PDBsum]</span></td></tr> | ||
<table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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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> | 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 | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
== References == | == References == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
[[Category: Alpert, T D | [[Category: Alpert, T D]] | ||
[[Category: Jez, J M | [[Category: Jez, J M]] | ||
[[Category: Kim, Y | [[Category: Kim, Y]] | ||
[[Category: Lee, S G | [[Category: Lee, S G]] | ||
[[Category: Nagata, A | [[Category: Nagata, A]] | ||
[[Category: Methyltransferase]] | [[Category: Methyltransferase]] | ||
[[Category: Parasite]] | [[Category: Parasite]] | ||
[[Category: Plasmodium]] | [[Category: Plasmodium]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 13:53, 4 January 2015
Phosphoethanolamine methyltransferase from Plasmodium falciparum in complex with SAH and phosphoethanolaminePhosphoethanolamine methyltransferase from Plasmodium falciparum in complex with SAH and phosphoethanolamine
Structural highlights
Publication Abstract from PubMedIn 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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