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| | ==Crystal structure of IspH in complex with iso-HMBPP== | | ==Crystal structure of IspH in complex with iso-HMBPP== |
| - | <StructureSection load='4eb3' size='340' side='right' caption='[[4eb3]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4eb3' size='340' side='right'caption='[[4eb3]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4eb3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EB3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EB3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4eb3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EB3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0O3:3-(HYDROXYMETHYL)BUT-3-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>0O3</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0O3:3-(HYDROXYMETHYL)BUT-3-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>0O3</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3f7t|3f7t]], [[3dnf|3dnf]], [[3ke8|3ke8]]</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=4eb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eb3 OCA], [https://pdbe.org/4eb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eb3 RCSB], [https://www.ebi.ac.uk/pdbsum/4eb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eb3 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ispH, lytB, yaaE, b0029, JW0027 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/4-hydroxy-3-methylbut-2-enyl_diphosphate_reductase 4-hydroxy-3-methylbut-2-enyl diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.1.2 1.17.1.2] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eb3 OCA], [http://pdbe.org/4eb3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eb3 RCSB], [http://www.ebi.ac.uk/pdbsum/4eb3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eb3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ISPH_ECOLI ISPH_ECOLI]] Converts 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Is also involved in penicillin tolerance and control of the stringent response. Seems to directly or indirectly interact with RelA to maintain it in an inactive form during normal growth.<ref>PMID:19569147</ref> <ref>PMID:20080550</ref> <ref>PMID:22137895</ref> | + | [[https://www.uniprot.org/uniprot/ISPH_ECOLI ISPH_ECOLI]] Converts 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Is also involved in penicillin tolerance and control of the stringent response. Seems to directly or indirectly interact with RelA to maintain it in an inactive form during normal growth.<ref>PMID:19569147</ref> <ref>PMID:20080550</ref> <ref>PMID:22137895</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4eb3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4eb3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[4-hydroxy-3-methylbut-2-enyl diphosphate reductase 3D structures|4-hydroxy-3-methylbut-2-enyl diphosphate reductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 4-hydroxy-3-methylbut-2-enyl diphosphate reductase]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Ecoli]] | + | [[Category: Large Structures]] |
| - | [[Category: Bacher, A]] | + | [[Category: Bacher A]] |
| - | [[Category: Groll, M]] | + | [[Category: Groll M]] |
| - | [[Category: Oldfield, E]] | + | [[Category: Oldfield E]] |
| - | [[Category: Span, I]] | + | [[Category: Span I]] |
| - | [[Category: Wang, K]] | + | [[Category: Wang K]] |
| - | [[Category: Wang, W]] | + | [[Category: Wang W]] |
| - | [[Category: Iron-sulfur protein]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Reductase]]
| + | |
| Structural highlights
Function
[ISPH_ECOLI] Converts 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Is also involved in penicillin tolerance and control of the stringent response. Seems to directly or indirectly interact with RelA to maintain it in an inactive form during normal growth.[1] [2] [3]
Publication Abstract from PubMed
The [4Fe-4S] protein IspH in the methylerythritol phosphate isoprenoid biosynthesis pathway is an important anti-infective drug target, but its mechanism of action is still the subject of debate. Here, by using electron paramagnetic resonance (EPR) spectroscopy and (2)H, (17)O, and (57)Fe isotopic labeling, we have characterized and assigned two key reaction intermediates in IspH catalysis. The results are consistent with the bioorganometallic mechanism proposed earlier, and the mechanism is proposed to have similarities to that of ferredoxin, thioredoxin reductase, in that one electron is transferred to the [4Fe-4S](2+) cluster, which then performs a formal two-electron reduction of its substrate, generating an oxidized high potential iron-sulfur protein (HiPIP)-like intermediate. The two paramagnetic reaction intermediates observed correspond to the two intermediates proposed in the bioorganometallic mechanism: the early pi-complex in which the substrate's 3-CH(2)OH group has rotated away from the reduced iron-sulfur cluster, and the next, eta(3)-allyl complex formed after dehydroxylation. No free radical intermediates are observed, and the two paramagnetic intermediates observed do not fit in a Birch reduction-like or ferraoxetane mechanism. Additionally, we show by using EPR spectroscopy and X-ray crystallography that two substrate analogues (4 and 5) follow the same reaction mechanism.
Are free radicals involved in IspH catalysis? An EPR and crystallographic investigation.,Wang W, Wang K, Span I, Jauch J, Bacher A, Groll M, Oldfield E J Am Chem Soc. 2012 Jul 11;134(27):11225-34. doi: 10.1021/ja303445z. Epub 2012, Jun 28. PMID:22687151[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Grawert T, Rohdich F, Span I, Bacher A, Eisenreich W, Eppinger J, Groll M. Structure of active IspH enzyme from Escherichia coli provides mechanistic insights into substrate reduction. Angew Chem Int Ed Engl. 2009;48(31):5756-9. PMID:19569147 doi:10.1002/anie.200900548
- ↑ Grawert T, Span I, Eisenreich W, Rohdich F, Eppinger J, Bacher A, Groll M. Probing the reaction mechanism of IspH protein by x-ray structure analysis. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1077-81. Epub 2009 Dec 28. PMID:20080550
- ↑ Span I, Grawert T, Bacher A, Eisenreich W, Groll M. Crystal Structures of Mutant IspH Proteins Reveal a Rotation of the Substrate's Hydroxymethyl Group during Catalysis. J Mol Biol. 2011 Nov 23. PMID:22137895 doi:10.1016/j.jmb.2011.11.033
- ↑ Wang W, Wang K, Span I, Jauch J, Bacher A, Groll M, Oldfield E. Are free radicals involved in IspH catalysis? An EPR and crystallographic investigation. J Am Chem Soc. 2012 Jul 11;134(27):11225-34. doi: 10.1021/ja303445z. Epub 2012, Jun 28. PMID:22687151 doi:http://dx.doi.org/10.1021/ja303445z
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