2c82
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X-RAY STRUCTURE OF 1-DEOXY-D-XYLULOSE 5-PHOSPHATE REDUCTOISOMERASE, DXR, RV2870C, FROM MYCOBACTERIUM TUBERCULOSIS
OverviewOverview
1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzes the, NADPH-dependent rearrangement and reduction of 1-deoxy-D-xylulose, 5-phosphate to form 2-C-methyl-D-erythritol 4-phosphate, as the second, step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway, found in many bacteria and plants. The end product, isopentenyl, diphosphate, is the precursor of various isoprenoids vital to all living, organisms. The pathway is not found in humans; the mevalonate pathway is, instead used for the formation of isopentenyl diphosphate. This, difference, combined with its essentiality, makes the reductoisomerase an, excellent drug target in a number of pathogenic organisms. The structure, of 1-deoxy-D-xylulose 5-phosphate reductoisomerase from Mycobacterium, tuberculosis (Rv2870c) was solved by molecular replacement and refined to, a resolution of 1.9 A. The enzyme exhibited an estimated kcat of 5.3 s-1, and Km and kcat/Km values of 7.2 microM and 7.4x10(5) M-1 s-1 for NADPH, and 340 microM and 1.6x10(4) M-1 s-1 for 1-deoxy-D-xylulose 5-phosphate., In the structure, a sulfate is bound at the expected site of the phosphate, moiety of the sugar substrate. The M. tuberculosis enzyme displays a, similar fold to the previously published structures from Escherichia coli, and Zymomonas mobilis. Comparisons offer suggestions for the design of, specific drugs. Furthermore, the new structure represents an intermediate, conformation between the open apo form and the closed holo form observed, previously, giving insights into the conformational changes associated, with catalysis.
About this StructureAbout this Structure
2C82 is a Single protein structure of sequence from Mycobacterium tuberculosis with SO4 as ligand. Active as 1-deoxy-D-xylulose-5-phosphate reductoisomerase, with EC number 1.1.1.267 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
The 1.9 A resolution structure of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a potential drug target., Henriksson LM, Bjorkelid C, Mowbray SL, Unge T, Acta Crystallogr D Biol Crystallogr. 2006 Jul;62(Pt 7):807-13. Epub 2006, Jun 20. PMID:16790937
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