6fqy | pdb_00006fqy

Plasmodium falciparum 6-phosphogluconate dehydrogenase in its apo form, in complex with its cofactor NADP+ and in complex with its substrate 6-phosphogluconate

spinqualitylabelsall models 6fqy, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6fqy is a 2 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Ligands: EDO, NAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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] 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 6-phosphogluconate dehydrogenase 3D structures

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