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==Crystal structure of the sugar phosphatase PfHAD1 from Plasmodium falciparum==
==Crystal structure of the sugar phosphatase PfHAD1 from Plasmodium falciparum==
<StructureSection load='4qjb' size='340' side='right' caption='[[4qjb]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
<StructureSection load='4qjb' size='340' side='right'caption='[[4qjb]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4qjb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QJB FirstGlance]. <br>
<table><tr><td colspan='2'>[[4qjb]] 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=4QJB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QJB FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><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]] 2.05&#8491;</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=4qjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qjb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qjb RCSB], [http://www.ebi.ac.uk/pdbsum/4qjb PDBsum]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<table>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4qjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qjb OCA], [https://pdbe.org/4qjb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qjb RCSB], [https://www.ebi.ac.uk/pdbsum/4qjb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qjb ProSAT]</span></td></tr>
<div style="background-color:#fffaf0;">
</table>
== Publication Abstract from PubMed ==
== Function ==
Isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway generates commercially important products and is a target for antimicrobial drug development. MEP pathway regulation is poorly understood in microorganisms. Here we employ a forward genetics approach to understand MEP pathway regulation in the malaria parasite, Plasmodium falciparum. The antimalarial fosmidomycin inhibits the MEP pathway enzyme deoxyxylulose 5-phosphate reductoisomerase (DXR). Fosmidomycin-resistant P. falciparum are enriched for changes in the PF3D7_1033400 locus (hereafter referred to as PfHAD1), encoding a homologue of haloacid dehalogenase (HAD)-like sugar phosphatases. We describe the structural basis for loss-of-function PfHAD1 alleles and find that PfHAD1 dephosphorylates a variety of sugar phosphates, including glycolytic intermediates. Loss of PfHAD1 is required for fosmidomycin resistance. Parasites lacking PfHAD1 have increased MEP pathway metabolites, particularly the DXR substrate, deoxyxylulose 5-phosphate. PfHAD1 therefore controls substrate availability to the MEP pathway. Because PfHAD1 has homologues in plants and bacteria, other HAD proteins may be MEP pathway regulators.
[https://www.uniprot.org/uniprot/Q8IJ74_PLAF7 Q8IJ74_PLAF7]
 
A sugar phosphatase regulates the methylerythritol phosphate (MEP) pathway in malaria parasites.,Guggisberg AM, Park J, Edwards RL, Kelly ML, Hodge DM, Tolia NH, Odom AR Nat Commun. 2014 Jul 24;5:4467. doi: 10.1038/ncomms5467. PMID:25058848<ref>PMID:25058848</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Park, J.]]
[[Category: Large Structures]]
[[Category: Tolia, N H.]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Had rossmanoid fold]]
[[Category: Park J]]
[[Category: Had-like hydrolase]]
[[Category: Tolia NH]]
[[Category: Hydrolase]]
[[Category: Sugar phosphatase]]
[[Category: Three-layered alpha-beta-alpha sandwich]]
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