IspG: Difference between revisions

Revision as of 16:02, 30 November 2017

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 anti-tuberculosis and antimalarial drugs^[2].

Structural highlights

The substrate of IpsG. and its ^[3].

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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 30-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

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
↑ 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:http://dx.doi.org/10.1016/j.febslet.2012.07.070

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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

[3] 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:http://dx.doi.org/10.1016/j.febslet.2012.07.070

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 == Structural highlights ==
-The substrate <scene name='77/774679/Cv/2'>MEcPP is located in the cavity between the TIM-barrel and the lid domain</scene> of IpsG.  <scene name='77/774679/Cv/3'>It binds covalently to the 4Fe4S cluster</scene> and its <scene name='77/774679/Cv/4'>PP moiety binds to 2 Arg sidechains</scene><ref>PMID:22967895</ref>.
+The substrate <scene name='77/774679/Cv/2'>MEcPP is located in the cavity between the TIM-barrel and the lid domain</scene> of IpsG.  <scene name='77/774679/Cv/3'>It binds covalently to the 4Fe4S cluster</scene> and its <scene name='77/774679/Cv/8'>PP moiety binds to 4 Arg and 1 Lys sidechains</scene><ref>PMID:22967895</ref>.
+*<scene name='77/774679/Cv/6'>4Fe4S cluster binding site</scene>.
+*<scene name='77/774679/Cv/7'>Whole active site</scene>.
 </StructureSection>
 == 3D Structures of IspG ==