2xwn

Crystal structure of IspD from Mycobacterium tuberculosis in complex with CTP and Mg

spinqualitylabelsall models 2xwn, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xwn is a 2 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CTP, MG Related: 2xwm, 2xwl Activity: 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase, with EC number 2.7.7.60 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ISPD_MYCTU] Catalyzes the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from CTP and 2-C-methyl-D-erythritol 4-phosphate (MEP) (By similarity). Publication Abstract from PubMed A number of pathogens, including the causative agents of tuberculosis and malaria, synthesize isopentenyl diphosphate via the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway rather than the classical mevalonate pathway found in humans. As part of a structure-based drug-discovery program against tuberculosis, IspD, the enzyme that carries out the third step in the MEP pathway, was targeted. Constructs of both the Mycobacterium smegmatis and the Mycobacterium tuberculosis enzymes that were suitable for structural and inhibitor-screening studies were engineered. Two crystal structures of the M. smegmatis enzyme were produced, one in complex with CTP and the other in complex with CMP. In addition, the M. tuberculosis enzyme was crystallized in complex with CTP. Here, the structure determination and crystallographic refinement of these crystal forms and the enzymatic characterization of the M. tuberculosis enzyme construct are reported. A comparison with known IspD structures allowed the definition of the structurally conserved core of the enzyme. It indicates potential flexibility in the enzyme and in particular in areas close to the active site. These well behaved constructs provide tools for future target-based screening of potential inhibitors. The conserved nature of the extended active site suggests that any new inhibitor will potentially exhibit broad-spectrum activity. Structural and functional studies of mycobacterial IspD enzymes.,Bjorkelid C, Bergfors T, Henriksson LM, Stern AL, Unge T, Mowbray SL, Jones TA Acta Crystallogr D Biol Crystallogr. 2011 May;67(Pt 5):403-14. Epub 2011, Apr 8. PMID:21543842 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also MEP cytidylyltransferase

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