3wqq | pdb_00003wqq

Crystal structure of PfDXR complexed with inhibitor-3

spinqualitylabelsall models 3wqq, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3wqq is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, IB3, MG, NDP Related: 3wqr, 3wqs Activity: 1-deoxy-D-xylulose-5-phosphate reductoisomerase, with EC number 1.1.1.267 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed 1-Deoxy-d-xylulose 5-phosphate reductoisomerase of Plasmodium falciparum (PfIspC, PfDxr), believed to be the rate-limiting enzyme of the nonmevalonate pathway of isoprenoid biosynthesis (MEP pathway), is a clinically validated antimalarial target. The enzyme is efficiently inhibited by the natural product fosmidomycin. To gain new insights into the structure activity relationships of reverse fosmidomycin analogs, several reverse analogs of fosmidomycin were synthesized and biologically evaluated. The 4-methoxyphenyl substituted derivative 2c showed potent inhibition of PfIspC as well as of P. falciparum growth and was more than one order of magnitude more active than fosmidomycin. The binding modes of three new derivatives in complex with PfIspC, reduced nicotinamide adenine dinucleotide phosphate, and Mg(2+) were determined by X-ray structure analysis. Notably, PfIspC selectively binds the S-enantiomers of the study compounds. Binding Modes of Reverse Fosmidomycin Analogs toward the Antimalarial Target IspC.,Konzuch S, Umeda T, Held J, Hahn S, Brucher K, Lienau C, Behrendt CT, Grawert T, Bacher A, Illarionov B, Fischer M, Mordmuller B, Tanaka N, Kurz T J Med Chem. 2014 Nov 13;57(21):8827-38. doi: 10.1021/jm500850y. Epub 2014 Oct 20. PMID:25254502 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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