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4qjb
From Proteopedia
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<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><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> | ||
<table> | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 06:19, 13 August 2014
Crystal structure of the sugar phosphatase PfHAD1 from Plasmodium falciparum
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