2XWL
Crystal structure of IspD from Mycobacterium smegmatis in complex with CTP and Mg
Summary for 2XWL
| Entry DOI | 10.2210/pdb2xwl/pdb |
| Related | 2XWM 2XWN |
| Descriptor | 2-C-METHYL-D-ERYTHRITOL 4-PHOSPHATE CYTIDYLYLTRANSFERASE, MAGNESIUM ION, CYTIDINE-5'-TRIPHOSPHATE, ... (4 entities in total) |
| Functional Keywords | transferase, mep pathway |
| Biological source | MYCOBACTERIUM SMEGMATIS |
| Total number of polymer chains | 2 |
| Total formula weight | 46350.63 |
| Authors | Bjorkelid, C.,Bergfors, T.,Unge, T.,Jones, T.A. (deposition date: 2010-11-04, release date: 2011-04-27, Last modification date: 2023-12-20) |
| Primary citation | Bjorkelid, C.,Bergfors, T.,Henriksson, L.M.,Stern, A.L.,Unge, T.,Mowbray, S.L.,Jones, T.A. Structural and Functional Studies on Mycobacterial Ispd Enzymes Acta Crystallogr.,Sect.D, 67:403-, 2011 Cited by PubMed Abstract: 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. PubMed: 21543842DOI: 10.1107/S0907444911006160 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.49 Å) |
Structure validation
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