4kp7
From Proteopedia
Structure of Plasmodium IspC in complex with a beta-thia-isostere derivative of Fosmidomycin
Structural highlights
FunctionDXR_PLAFX Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).[1] Publication Abstract from PubMedThe emergence and spread of multidrug-resistant pathogens is widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the synthesis and properties of "reverse" thia-analogs of fosmidomycin, which inhibit the first committed enzyme of a metabolic pathway that is essential for the causative agents of tuberculosis and malaria but is absent in the human host. Notably, IspC displays a high level of enantioselectivity for an alpha-susbtituted fosmidomycin derivative. IspC as target for antiinfective drug discovery: Synthesis, enantiomeric separation and structural biology of fosmidomycin thia-isosters.,Kunfermann A, Lienau C, Illarionov B, Held J, Grawert T, Behrendt CT, Werner P, Hahn S, Eisenreich W, Riederer U, Mordmuller B, Bacher A, Fischer M, Groll M, Kurz T J Med Chem. 2013 Sep 13. PMID:24032981[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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