|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==IspH:HMBPP complex structure of E126Q mutant== | | ==IspH:HMBPP complex structure of E126Q mutant== |
| - | <StructureSection load='3szu' size='340' side='right' caption='[[3szu]], [[Resolution|resolution]] 1.40Å' scene=''> | + | <StructureSection load='3szu' size='340' side='right'caption='[[3szu]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3szu]] 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=3SZU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SZU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3szu]] 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=3SZU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SZU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F3S:FE3-S4+CLUSTER'>F3S</scene>, <scene name='pdbligand=H6P:(2E)-4-HYDROXY-3-METHYLBUT-2-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>H6P</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]] 1.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3f7t|3f7t]], [[3dnf|3dnf]], [[3szl|3szl]], [[3szo|3szo]], [[3t0f|3t0f]], [[3t0g|3t0g]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F3S:FE3-S4+CLUSTER'>F3S</scene>, <scene name='pdbligand=H6P:(2E)-4-HYDROXY-3-METHYLBUT-2-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>H6P</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3szu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3szu OCA], [https://pdbe.org/3szu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3szu RCSB], [https://www.ebi.ac.uk/pdbsum/3szu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3szu ProSAT]</span></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=3szu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3szu OCA], [http://pdbe.org/3szu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3szu RCSB], [http://www.ebi.ac.uk/pdbsum/3szu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3szu 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;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Isoprenoids derive from two universal precursors, isopentenyl diphosphate and dimethylallyl diphosphate, which in most human pathogens are synthesized in the deoxyxylulose phosphate pathway. The last step of this pathway is the conversion of (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate into a mixture of isopentenyl diphosphate and dimethylallyl diphosphate catalyzed by the iron-sulfur protein IspH. The crystal structures reported here of the IspH mutant proteins T167C, E126D and E126Q reveal an alternative substrate conformation compared to the wild-type structure. Thus, the previously observed alkoxide complex decomposes, and the substrate's hydroxymethyl group rotates to interact with Glu126. The carboxyl group of Glu126 then donates a proton to the hydroxyl group to enable water elimination. The structural and functional studies provide further knowledge of the IspH reaction mechanism, which opens up new routes to inhibitor design against malaria and tuberculosis.
| + | |
| - | | + | |
| - | Crystal Structures of Mutant IspH Proteins Reveal a Rotation of the Substrate's Hydroxymethyl Group during Catalysis.,Span I, Grawert T, Bacher A, Eisenreich W, Groll M J Mol Biol. 2011 Nov 23. PMID:22137895<ref>PMID:22137895</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3szu" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[4-hydroxy-3-methylbut-2-enyl diphosphate reductase|4-hydroxy-3-methylbut-2-enyl diphosphate reductase]] | + | *[[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: Eisenreich, W]] | + | [[Category: Eisenreich W]] |
| - | [[Category: Graewert, T]] | + | [[Category: Graewert T]] |
| - | [[Category: Groll, M]] | + | [[Category: Groll M]] |
| - | [[Category: Span, I]] | + | [[Category: Span I]] |
| - | [[Category: 3fe-4s iron-sulfur cluster]]
| + | |
| - | [[Category: Conserved cysteine]]
| + | |
| - | [[Category: Ipp and dmapp production final step]]
| + | |
| - | [[Category: Non-mevalonate pathway]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Substrate hmbpp]]
| + | |
