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| <StructureSection load='' size='340' side='right' caption='IspG containing 4Fe4S cluster complex with MEcPP, MES, K+ (purple) and Cl- (green) ions (PDB entry [[4g9p]])' scene=''> | | <StructureSection load='4g9p' size='340' side='right' caption='IspG containing 4Fe4S cluster complex with MEcPP, MES, K+ (purple) and Cl- (green) ions (PDB entry [[4g9p]])' scene=''> |
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Revision as of 17:49, 28 November 2017
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Function
IspG 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).
Relevance
The non-mevalonate enzymes are a target for tuberculostatic and antimalarial drugs[2].
Structural highlights
The 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 2 Arg sidechains[3].
- ↑ 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:https://dx.doi.org/10.1073/pnas.1121107109
- ↑ Rekittke I, Jomaa H, Ermler U. Structure of the GcpE (IspG)-MEcPP complex from Thermus thermophilus. FEBS Lett. 2012 Sep 21;586(19):3452-7. doi: 10.1016/j.febslet.2012.07.070. Epub, 2012 Aug 9. PMID:22967895 doi:https://dx.doi.org/10.1016/j.febslet.2012.07.070
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3D Structures of IspG
Updated on 28-November-2017
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
4s3c – TtIspG + PPi
4s3e, 4s3f – TtIspG + inhibitor
References
