3utc: Difference between revisions

Latest revision as of 10:25, 13 August 2026

Ec_IspH in complex with (E)-4-hydroxybut-3-enyl diphosphate

Structural highlights

3utc is a 2 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:	0JX
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 final step of the methylerythritol phosphate isoprenoid biosynthesis pathway is catalysed by the iron-sulphur enzyme IspH, producing the universal precursors of terpenes: isopentenyl diphosphate and dimethylallyl diphosphate. Here we report an unforeseen reaction discovered during the investigation of the interaction of IspH with acetylene inhibitors by X-ray crystallography, Mossbauer, and nuclear magnetic resonance spectroscopy. In addition to its role as a 2H(+)/2e(-) reductase, IspH can hydrate acetylenes to aldehydes and ketones via anti-Markovnikov/Markovnikov addition. The reactions only occur with the oxidised protein and proceed via eta(1)-O-enolate intermediates. One of these is characterized crystallographically and contains a C4 ligand oxygen bound to the unique, fourth iron in the 4Fe-4S cluster: this intermediate subsequently hydrolyzes to produce an aldehyde product. This unexpected side to IspH reactivity is of interest in the context of the mechanism of action of other acetylene hydratases, as well as in the design of antiinfectives targeting IspH.

Discovery of acetylene hydratase activity of the iron-sulphur protein IspH.,Span I, Wang K, Wang W, Zhang Y, Bacher A, Eisenreich W, Li K, Schulz C, Oldfield E, Groll M Nat Commun. 2012 Sep 4;3:1042. doi: 10.1038/ncomms2052. PMID:22948824^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Span I, Wang K, Wang W, Zhang Y, Bacher A, Eisenreich W, Li K, Schulz C, Oldfield E, Groll M. Discovery of acetylene hydratase activity of the iron-sulphur protein IspH. Nat Commun. 2012 Sep 4;3:1042. doi: 10.1038/ncomms2052. PMID:22948824 doi:https://dx.doi.org/10.1038/ncomms2052

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] Span I, Wang K, Wang W, Zhang Y, Bacher A, Eisenreich W, Li K, Schulz C, Oldfield E, Groll M. Discovery of acetylene hydratase activity of the iron-sulphur protein IspH. Nat Commun. 2012 Sep 4;3:1042. doi: 10.1038/ncomms2052. PMID:22948824 doi:https://dx.doi.org/10.1038/ncomms2052

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[2]

[3]

[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='3utc' size='340' side='right'caption='[[3utc]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3utc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UTC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3utc]] 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=3UTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UTC FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0JX:(3E)-4-HYDROXYBUT-3-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>0JX</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ke8|3ke8]], [[3dnf|3dnf]], [[3urk|3urk]], [[3utd|3utd]], [[3uv3|3uv3]], [[3uv6|3uv6]], [[3uv7|3uv7]], [[3uv8|3uv8]], [[3uwm|3uwm]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0JX:(3E)-4-HYDROXYBUT-3-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>0JX</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ispH, lytB, yaaE, b0029, JW0027 ([https://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'>[https://en.wikipedia.org/wiki/4-hydroxy-3-methylbut-2-enyl_diphosphate_reductase 4-hydroxy-3-methylbut-2-enyl diphosphate reductase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3utc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3utc OCA], [https://pdbe.org/3utc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3utc RCSB], [https://www.ebi.ac.uk/pdbsum/3utc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3utc ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[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>
+[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;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 26: @@
 __TOC__
 </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: Eisenreich, W]]
+[[Category: Eisenreich W]]
-[[Category: Groll, M]]
+[[Category: Groll M]]
-[[Category: Li, K]]
+[[Category: Li K]]
-[[Category: Oldfield, E]]
+[[Category: Oldfield E]]
-[[Category: Schulz, C]]
+[[Category: Schulz C]]
-[[Category: Span, I]]
+[[Category: Span I]]
-[[Category: Wang, K]]
+[[Category: Wang K]]
-[[Category: Wang, W]]
+[[Category: Wang W]]
-[[Category: Zhang, Y]]
+[[Category: Zhang Y]]
-[[Category: Iron-sulfur protein]]
-[[Category: Isoprenoid biosynthesis]]
-[[Category: Isph]]
-[[Category: Lytb]]
-[[Category: Non-mevalonate pathway]]
-[[Category: Oxidoreductase]]

3utc: Difference between revisions

Latest revision as of 10:25, 13 August 2026

Ec_IspH in complex with (E)-4-hydroxybut-3-enyl diphosphate

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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