DXP reductoisomerase
FunctionDXP reductoisomerase (DXR) or 1-deoxy-D-xylulose-5-phosphate reductoisomerase or IspC catalyzes the conversion of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate. DXR is part of the nonmevalonate pathway which synthesizes isoprenoids which are essential components of bacterial cell wall. NADPH is a cofactor of the reaction. Divalent metal cations (Mg+2, Mn+2) are involved in binding of the DXP substrate to DXR.[1] DiseaseThe antibiotic fosmidomycin is a structural analog of 2-C-methyl-D-erythritol 4-phosphate is a powerful inhibitor of DXR and is used as an anti-malaria drug. Structural highlightsDXR contains Mn+2 cation and the product analog fosmidomycin. (water molecules shown as red spheres).[2] 3D Structures of DXP reductoisomeraseDXP reductoisomerase 3D Structures
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ReferencesReferences
- ↑ Takahashi S, Kuzuyama T, Watanabe H, Seto H. A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9879-84. PMID:9707569
- ↑ Jansson AM, Wieckowska A, Bjorkelid C, Yahiaoui S, Sooriyaarachchi S, Lindh M, Bergfors T, Dharavath S, Desroses M, Suresh S, Andaloussi M, Nikhil R, Sreevalli S, Srinivasa BR, Larhed M, Jones TA, Karlen A, Mowbray SL. DXR inhibition by potent mono- and disubstituted fosmidomycin analogues. J Med Chem. 2013 Aug 8;56(15):6190-9. doi: 10.1021/jm4006498. Epub 2013 Jul 17. PMID:23819803 doi:http://dx.doi.org/10.1021/jm4006498