2y1d

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 and manganese.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 and manganese.

Structural highlights 2y1d is a 2 chain structure with sequence from Mycobacterium tuberculosis H37Rv. 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: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. See Also DXP reductoisomerase 3D Structures

spinqualitylabelsall models 2y1d, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image