IspG: Difference between revisions
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<StructureSection load='' size=' | <StructureSection load='4g9p' size='400' side='right' caption='IspG containing 4Fe4S cluster complex with MEcPP, MES, K+ (purple) and Cl- (green) ions (PDB entry [[4g9p]])' scene='77/774679/Cv/1'> | ||
== Function == | == 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 <ref>PMID:20932974</ref>. 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). | '''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 <ref>PMID:20932974</ref>. 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 == | == Relevance == | ||
The non-mevalonate enzymes are a target for | The non-mevalonate enzymes are a target for anti-tuberculosis and antimalarial drugs<ref>PMID:22586085</ref>. | ||
== Structural highlights == | == 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 | 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>. | ||
*<scene name='77/774679/Cv/6'>4Fe4S cluster binding site</scene>. | |||
*<scene name='77/774679/Cv/7'>Whole active site</scene>. | |||
*<scene name='77/774679/Cv/9'>1st Cl coordination site</scene>. | |||
*<scene name='77/774679/Cv/10'>Cl/K cluster coordination site</scene>. | |||
</StructureSection> | </StructureSection> | ||
== 3D Structures of IspG == | == 3D Structures of IspG == | ||
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[[4s39]], [[4s23]] – TtIspG + HMBPP <br /> | [[4s39]], [[4s23]] – TtIspG + HMBPP <br /> | ||
[[4s3a]], [[4s3b]], [[4s3c]] – TtIspG + intermediate <br /> | [[4s3a]], [[4s3b]], [[4s3c]] – TtIspG + intermediate <br /> | ||
[[ | [[4s3d]] – TtIspG + PPi <br /> | ||
[[4s3e]], [[4s3f]] – TtIspG + inhibitor <br /> | [[4s3e]], [[4s3f]] – TtIspG + inhibitor <br /> | ||
Latest revision as of 12:15, 12 June 2023
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 of IpsG. and its .
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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