View source for 6fqx


==Plasmodium falciparum 6-phosphogluconate dehydrogenase in its apo form, in complex with its cofactor NADP+ and in complex with its substrate 6-phosphogluconate==
<StructureSection load='6fqx' size='340' side='right'caption='[[6fqx]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fqx]] is a 8 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=6FQX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FQX 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AE3:2-(2-ETHOXYETHOXY)ETHANOL'>AE3</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=6fqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fqx OCA], [https://pdbe.org/6fqx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fqx RCSB], [https://www.ebi.ac.uk/pdbsum/6fqx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fqx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8IKT2_PLAF7 Q8IKT2_PLAF7] Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.[PIRNR:PIRNR000109]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The enzyme 6-phosphogluconate dehydrogenase (6PGD) of the malaria parasite Plasmodium falciparum catalyzes the third step of the pentose phosphate pathway converting 6-phosphogluconate (6PG) to ribulose 5-phosphate. The NADPH produced by 6PGD is crucial for antioxidant defense and redox regulation, and ribose 5-phosphate is essential for DNA and RNA synthesis in the rapidly growing parasite. Thus, 6PGD represents an attractive antimalarial drug target. In this study, we present the X-ray structures of Pf6PGD in native form as well as in complex with 6PG or nicotinamide adenine dinucleotide phosphate (NADP(+)) at resolutions of 2.8, 1.9, and 2.9A, respectively. The overall structure of the protein is similar to structures of 6PGDs from other species; however, a flexible loop close to the active site rearranges upon binding of 6PG and likely regulates the conformation of the cofactor NADP(+). Upon binding of 6PG, the active site loop adopts a closed conformation. In the absence of 6PG, the loop opens and NADP(+) is bound in a waiting position, indicating that the cofactor and 6PG bind independently from each other. This sequential binding mechanism was supported by kinetic studies on the homodimeric wild-type Pf6PGD. Furthermore, the function of the Plasmodium-specific residue W104L mutant was characterized by site-directed mutagenesis. Notably, the activity of Pf6PGD was found to be post-translationally redox regulated via S-nitrosylation, and screening the Medicines for Malaria Venture Malaria Box identified several compounds with IC50s in the low micromolar range. Together with the three-dimensional structure of the protein, this is a promising starting point for further drug discovery approaches.

Characterization of Plasmodium falciparum 6-Phosphogluconate Dehydrogenase as an Antimalarial Drug Target.,Haeussler K, Fritz-Wolf K, Reichmann M, Rahlfs S, Becker K J Mol Biol. 2018 Aug 8. pii: S0022-2836(18)30513-8. doi:, 10.1016/j.jmb.2018.07.030. PMID:30098336<ref>PMID:30098336</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 6fqx" style="background-color:#fffaf0;"></div>

==See Also==
*[[6-phosphogluconate dehydrogenase 3D structures|6-phosphogluconate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Becker K]]
[[Category: Fritz-Wolf K]]
[[Category: Haeussler K]]
[[Category: Rahlfs S]]
[[Category: Reichmann M]]