View source for 4s38


==IspG in complex MEcPP==
<StructureSection load='4s38' size='340' side='right'caption='[[4s38]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4s38]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S38 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S38 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CDI:2C-METHYL-D-ERYTHRITOL+2,4-CYCLODIPHOSPHATE'>CDI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4s38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s38 OCA], [https://pdbe.org/4s38 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s38 RCSB], [https://www.ebi.ac.uk/pdbsum/4s38 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s38 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ISPG_THET8 ISPG_THET8] Converts 2C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-2,4cPP) into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
IspG is the penultimate enzyme in non-mevalonate biosynthesis of the universal terpene building blocks isopentenyl diphosphate and dimethylallyl diphosphate. Its mechanism of action has been the subject of numerous studies but remained unresolved due to difficulties in identifying distinct reaction intermediates. Using a moderate reducing agent and an epoxide substrate analogue, we were now able to trap and crystallographically characterize various stages in the IspG-catalyzed conversion of 2-C-methyl-d-erythritol-2,4-cyclo-diphosphate into (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate. In addition, the enzyme's structure was determined in complex with several inhibitors. These results, combined with recent electron paramagnetic resonance data, allowed us to deduce a detailed and complete IspG catalytic mechanism, which describes all stages from initial ring opening to formation of (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate via discrete radical and carbanion intermediates. The data presented in this article provide a guide for the design of selective drugs against many prokaryotic and eukaryotic pathogens to which the non-mevalonate pathway is essential for survival and virulence.

Atomic-Resolution Structures of Discrete Stages on the Reaction Coordinate of the [FeS] Enzyme IspG (GcpE).,Quitterer F, Frank A, Wang K, Rao G, O'Dowd B, Li J, Guerra F, Abdel-Azeim S, Bacher A, Eppinger J, Oldfield E, Groll M J Mol Biol. 2015 Apr 11. pii: S0022-2836(15)00225-9. doi:, 10.1016/j.jmb.2015.04.002. PMID:25868383<ref>PMID:25868383</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4s38" style="background-color:#fffaf0;"></div>

==See Also==
*[[IspG|IspG]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Thermus thermophilus HB8]]
[[Category: Abdel-Azeim S]]
[[Category: Bacher A]]
[[Category: Eppinger J]]
[[Category: Frank A]]
[[Category: Groll M]]
[[Category: Guerra F]]
[[Category: Guodong R]]
[[Category: Li J]]
[[Category: O'Dowd B]]
[[Category: Oldfield E]]
[[Category: Quitterer F]]
[[Category: Wang K]]