View source for 7myv


==Plasmodium falciparum HAD5/PMM==
<StructureSection load='7myv' size='340' side='right'caption='[[7myv]], [[Resolution|resolution]] 3.51&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7myv]] 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=7MYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MYV 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]] 3.51&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7myv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7myv OCA], [https://pdbe.org/7myv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7myv RCSB], [https://www.ebi.ac.uk/pdbsum/7myv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7myv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8IJM5_PLAF7 Q8IJM5_PLAF7] Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.[RuleBase:RU361118]
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== Publication Abstract from PubMed ==
The malaria-causing parasite Plasmodium falciparum is responsible for over 200 million infections and 400,000 deaths per year. At multiple stages during its complex life cycle, P. falciparum expresses several essential proteins tethered to its surface by glycosylphosphatidylinositol (GPI) anchors, which are critical for biological processes such as parasite egress and reinvasion of host red blood cells. Targeting this pathway therapeutically has the potential to broadly impact parasite development across several life stages. Here, we characterize an upstream component of parasite GPI anchor biosynthesis, the putative phosphomannomutase (PMM) (EC 5.4.2.8), HAD5 (PF3D7_1017400). We confirmed the PMM and phosphoglucomutase activities of purified recombinant HAD5 by developing novel linked enzyme biochemical assays. By regulating the expression of HAD5 in transgenic parasites with a TetR-DOZI-inducible knockdown system, we demonstrated that HAD5 is required for malaria parasite egress and erythrocyte reinvasion, and we assessed the role of HAD5 in GPI anchor synthesis by autoradiography of radiolabeled glucosamine and thin layer chromatography. Finally, we determined the three-dimensional X-ray crystal structure of HAD5 and identified a substrate analog that specifically inhibits HAD5 compared to orthologous human PMMs in a time-dependent manner. These findings demonstrate that the GPI anchor biosynthesis pathway is exceptionally sensitive to inhibition in parasites and that HAD5 has potential as a specific, multistage antimalarial target.

Enzymatic and structural characterization of HAD5, an essential phosphomannomutase of malaria-causing parasites.,Frasse PM, Miller JJ, Polino AJ, Soleimani E, Zhu JS, Jakeman DL, Jez JM, Goldberg DE, Odom John AR J Biol Chem. 2022 Feb;298(2):101550. doi: 10.1016/j.jbc.2021.101550. Epub 2021, Dec 29. PMID:34973333<ref>PMID:34973333</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 7myv" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphomannomutase|Phosphomannomutase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Frasse PM]]
[[Category: Goldberg DE]]
[[Category: Odom John AR]]