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| | <StructureSection load='3zgl' size='340' side='right'caption='[[3zgl]], [[Resolution|resolution]] 1.68Å' scene=''> | | <StructureSection load='3zgl' size='340' side='right'caption='[[3zgl]], [[Resolution|resolution]] 1.68Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zgl]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZGL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZGL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zgl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZGL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=10E:(2E)-4-AMINO-3-METHYLBUT-2-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>10E</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=10E:(2E)-4-AMINO-3-METHYLBUT-2-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>10E</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zgl OCA], [http://pdbe.org/3zgl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zgl RCSB], [http://www.ebi.ac.uk/pdbsum/3zgl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zgl ProSAT]</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=3zgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zgl OCA], [https://pdbe.org/3zgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zgl RCSB], [https://www.ebi.ac.uk/pdbsum/3zgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zgl 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 == |
| 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
IspH, also called LytB, a protein involved in the biosynthesis of isoprenoids through the methylerythritol phosphate pathway, is an attractive target for the development of new antimicrobial drugs. Here, we report crystal structures of Escherichia coli IspH in complex with the two most potent inhibitors: (E)-4-mercapto-3-methylbut-2-en-1-yl diphosphate (TMBPP) and (E)-4-amino-3-methylbut-2-en-1-yl diphosphate (AMBPP) at 1.95 and 1.7 A resolution, respectively. The structure of the E. coli IspH:TMBPP complex exhibited two conformers of the inhibitor. This unexpected feature was exploited to design and evolve new antimicrobial candidates in silico.
Further Insight into Crystal Structures of Escherichia coli IspH/LytB in Complex with Two Potent Inhibitors of the MEP Pathway: A Starting Point for Rational Design of New Antimicrobials.,Borel F, Barbier E, Krasutsky S, Janthawornpong K, Chaignon P, Poulter CD, Ferrer JL, Seemann M Chembiochem. 2017 Nov 2;18(21):2137-2144. doi: 10.1002/cbic.201700363. Epub 2017 , Oct 2. PMID:28862365[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
- ↑ Borel F, Barbier E, Krasutsky S, Janthawornpong K, Chaignon P, Poulter CD, Ferrer JL, Seemann M. Further Insight into Crystal Structures of Escherichia coli IspH/LytB in Complex with Two Potent Inhibitors of the MEP Pathway: A Starting Point for Rational Design of New Antimicrobials. Chembiochem. 2017 Nov 2;18(21):2137-2144. doi: 10.1002/cbic.201700363. Epub 2017 , Oct 2. PMID:28862365 doi:http://dx.doi.org/10.1002/cbic.201700363
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