2y1f | pdb_00002y1f

X-RAY STRUCTURE OF 1-DEOXY-D-XYLULOSE 5-PHOSPHATE REDUCTOISOMERASE, DXR, RV2870C, FROM MYCOBACTERIUM TUBERCULOSIS, IN COMPLEX WITH A 3,4-DICHLOROPHENYL-SUBSTITUTED FOSMIDOMYCIN ANALOGUE, MANGANESE AND NADPH.

spinqualitylabelsall models 2y1f, resolution 1.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2y1f is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 34F, MN, NDP, SO4 Related: 2y1c, 2y1g, 2y1d, 2y1e Activity: 1-deoxy-D-xylulose-5-phosphate reductoisomerase, with EC number 1.1.1.267 Resources: FirstGlance, OCA, RCSB, PDBsum Function [A2VLK3_MYCTU] Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP) (By similarity).[HAMAP-Rule:MF_00183][SAAS:SAAS003821_004_013509] Publication Abstract from PubMed The natural antibiotic fosmidomycin acts via inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. Fosmidomycin is active on Mycobacterium tuberculosis DXR (MtDXR) but it lacks antibacterial activity, probably because of poor uptake. alpha-Aryl substituted fosmidomycin analogues have more favorable physicochemical properties, and are also more active in inhibiting malaria parasite growth. We have solved crystal structures of MtDXR in complex with 3,4-dichlorophenyl substituted fosmidomycin analogues; these show important differences compared to our previously described forsmidomycin-DXR complex. Our best inhibitor has an IC50 = 0.15 muM on MtDXR but still lacked activity in a mycobacterial growth assay (MICs > 32 mug/ml). The combined results, however, provide insights into how DXR accommodates the new inhibitors and serve as an excellent starting point for the design of other novel and more potent inhibitors, particularly against pathogens where uptake is less of a problem, such as the malaria parasite. Design, Synthesis and X-ray Crystallographic Studies of alpha-Aryl Substituted Fosmidomycin Analogues as Inhibitors of Mycobacterium tuberculosis 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase.,Andaloussi M, Henriksson LM, Wieckowska A, Lindh M, Bjorkelid C, Larsson AM, Suresh S, Iyer H, Srinivasa BR, Bergfors T, Unge T, Mowbray SL, Larhed ML, Jones AT, Karlen AB J Med Chem. 2011 Jun 16. PMID:21678907 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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