IspG

Function

IspG 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).

Relevance

The non-mevalonate enzymes are a target for anti-tuberculosis and antimalarial drugs^[2].

Structural highlights

The substrate of IpsG. and its .

.
.
.
.

IspG containing 4Fe4S cluster complex with MEcPP, MES, K+ (purple) and Cl- (green) ions (PDB entry 4g9p)

Drag the structure with the mouse to rotate

3D Structures of IspG3D 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

ReferencesReferences

↑ 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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Joel L. Sussman, Alexander Berchansky

[1] 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

[2] 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

[1]

[2]