1cet

CHLOROQUINE BINDS IN THE COFACTOR BINDING SITE OF PLASMODIUM FALCIPARUM LACTATE DEHYDROGENASE.

spinqualitylabelsall models 1cet, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1cet is a 1 chain structure with sequence from Plasmodium falciparum. The June 2008 RCSB PDB Molecule of the Month feature on Lactate Dehydrogenase by David S. Goodsell is 10.2210/rcsb_pdb/mom_2008_6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.05Å Ligands: CLQ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LDH_PLAFD Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Although the molecular mechanism by which chloroquine exerts its effects on the malarial parasite Plasmodium falciparum remains unclear, the drug has previously been found to interact specifically with the glycolytic enzyme lactate dehydrogenase from the parasite. In this study we have determined the crystal structure of the complex between chloroquine and P. falciparum lactate dehydrogenase. The bound chloroquine is clearly seen within the NADH binding pocket of the enzyme, occupying a position similar to that of the adenyl ring of the cofactor. Chloroquine hence competes with NADH for binding to the enzyme, acting as a competitive inhibitor for this critical glycolytic enzyme. Specific interactions between the drug and amino acids unique to the malarial form of the enzyme suggest this binding is selective. Inhibition studies confirm that chloroquine acts as a weak inhibitor of lactate dehydrogenase, with mild selectivity for the parasite enzyme. As chloroquine has been shown to accumulate to millimolar concentrations within the food vacuole in the gut of the parasite, even low levels of inhibition may contribute to the biological efficacy of the drug. The structure of this enzyme-inhibitor complex provides a template from which the quinoline moiety might be modified to develop more efficient inhibitors of the enzyme. Chloroquine binds in the cofactor binding site of Plasmodium falciparum lactate dehydrogenase.,Read JA, Wilkinson KW, Tranter R, Sessions RB, Brady RL J Biol Chem. 1999 Apr 9;274(15):10213-8. PMID:10187806 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lactate dehydrogenase 3D structures

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