IspG
From Proteopedia
FunctionIspG or 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase is a 4Fe4S protein which serves as the penultimate enzyme of the non-mevalonate pathway for the biosynthesis os isoprenoid precursors like isopentenyl diphosphate and dimethylallyl [1]. It catalyzes the ring opening of 2C-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP) producing (E)-1-hydroxyl-2-methyl-but-2-enyl-4-diphosphate (HMBPP). RelevanceThe non-mevalonate enzymes are a target for anti-tuberculosis and antimalarial drugs[2]. Structural highlightsThe substrate MEcPP is located in the cavity between the TIM-barrel and the lid domain of IpsG. It binds covalently to the 4Fe4S cluster and its PP moiety binds to 4 Arg and 1 Lys sidechains. |
|
3D Structures of IspG
Updated on 12-June-2023
3noy – IspG – Aquifex aeolicus
4mwa – IspG – Bacillus anthracis
2y0f – TtIspG – Thermus thermophilus
4s38, 4g9p – TtIspG + MEcPP
4s39, 4s23 – TtIspG + HMBPP
4s3a, 4s3b, 4s3c – TtIspG + intermediate
4s3d – TtIspG + PPi
4s3e, 4s3f – TtIspG + inhibitor
References
- ↑ Lee M, Grawert T, Quitterer F, Rohdich F, Eppinger J, Eisenreich W, Bacher A, Groll M. Biosynthesis of Isoprenoids: Crystal Structure of the [4Fe-4S] Cluster Protein IspG. J Mol Biol. 2010 Oct 7. PMID:20932974 doi:10.1016/j.jmb.2010.09.050
- ↑ Liu YL, Guerra F, Wang K, Wang W, Li J, Huang C, Zhu W, Houlihan K, Li Z, Zhang Y, Nair SK, Oldfield E. Structure, function and inhibition of the two- and three-domain 4Fe-4S IspG proteins. Proc Natl Acad Sci U S A. 2012 May 29;109(22):8558-63. doi:, 10.1073/pnas.1121107109. Epub 2012 May 14. PMID:22586085 doi:http://dx.doi.org/10.1073/pnas.1121107109