3WQS: Crystal Structure Of Pfdxr Complexed With Inhibitor-126

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.
PDB ID: 3WQSDownload
MMDB ID: 124980
PDB Deposition Date: 2014/1/31
Updated in MMDB: 2014/11
Experimental Method:
x-ray diffraction
Resolution: 2.35  Å
Source Organism:
Similar Structures:
Biological Unit for 3WQS: dimeric; determined by author and by software (PISA)
Molecular Components in 3WQS
Label Count Molecule
Proteins (2 molecules)
1-deoxy-d-xylulose 5-phosphate Reductoisomerase, Apicoplast
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

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