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| | ==Structural Basis of a Thiopeptide Antibiotic Multidrug Resistance System from Streptomyces lividans:Nosiheptide in Complex with TipAS== | | ==Structural Basis of a Thiopeptide Antibiotic Multidrug Resistance System from Streptomyces lividans:Nosiheptide in Complex with TipAS== |
| - | <StructureSection load='2mc0' size='340' side='right'caption='[[2mc0]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2mc0' size='340' side='right'caption='[[2mc0]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mc0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"actinomyces_lividans"_krasil'nikov_et_al._1965 "actinomyces lividans" krasil'nikov et al. 1965]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MC0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mc0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_actuosus Streptomyces actuosus] and [https://en.wikipedia.org/wiki/Streptomyces_lividans Streptomyces lividans]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MC0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO1:4-(HYDROXYMETHYL)-3-METHYL-1H-INDOLE-2-CARBOXYLIC+ACID'>NO1</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3GL:(2S,4S)-2-AMINO-4-HYDROXY-PENTANEDIOIC+ACID'>3GL</scene>, <scene name='pdbligand=BB9:(2Z)-2-AMINO-3-SULFANYLPROP-2-ENOIC+ACID'>BB9</scene>, <scene name='pdbligand=DBU:(2Z)-2-AMINOBUT-2-ENOIC+ACID'>DBU</scene>, <scene name='pdbligand=MH6:3-HYDROXY-2-IMINOPROPANOIC+ACID'>MH6</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=NO1:4-(HYDROXYMETHYL)-3-METHYL-1H-INDOLE-2-CARBOXYLIC+ACID'>NO1</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3GL:(2S,4S)-2-AMINO-4-HYDROXY-PENTANEDIOIC+ACID'>3GL</scene>, <scene name='pdbligand=BB9:(2Z)-2-AMINO-3-SULFANYLPROP-2-ENOIC+ACID'>BB9</scene>, <scene name='pdbligand=DBU:(2Z)-2-AMINOBUT-2-ENOIC+ACID'>DBU</scene>, <scene name='pdbligand=MH6:3-HYDROXY-2-IMINOPROPANOIC+ACID'>MH6</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
| + | |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ny9|1ny9]], [[2mbz|2mbz]]</div></td></tr>
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| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tipA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1916 "Actinomyces lividans" Krasil'nikov et al. 1965])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mc0 OCA], [https://pdbe.org/2mc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mc0 RCSB], [https://www.ebi.ac.uk/pdbsum/2mc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mc0 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=2mc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mc0 OCA], [https://pdbe.org/2mc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mc0 RCSB], [https://www.ebi.ac.uk/pdbsum/2mc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mc0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TIPA_STRLI TIPA_STRLI]] Transcriptional activator. Is activated when bound to the antibiotic thiostrepton.
| + | [https://www.uniprot.org/uniprot/TIPA_STRLI TIPA_STRLI] Transcriptional activator. Is activated when bound to the antibiotic thiostrepton. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Actinomyces lividans krasil'nikov et al. 1965]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allan, M G]] | + | [[Category: Streptomyces actuosus]] |
| - | [[Category: Grzesiek, S]] | + | [[Category: Streptomyces lividans]] |
| - | [[Category: Habazettl, J]] | + | [[Category: Allan MG]] |
| - | [[Category: Jensen, P]] | + | [[Category: Grzesiek S]] |
| - | [[Category: Sass, H]] | + | [[Category: Habazettl J]] |
| - | [[Category: Bacterial protein]] | + | [[Category: Jensen P]] |
| - | [[Category: Multidrug recognition]] | + | [[Category: Sass H]] |
| - | [[Category: Protein/thiopeptide]]
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| - | [[Category: Streptomyces lividan]]
| + | |
| - | [[Category: Tipas-nosiheptide complex]]
| + | |
| - | [[Category: Transcription activator-antibiotic complex]]
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| - | [[Category: Transcriptional activation]]
| + | |
| - | [[Category: Transcriptional activator-antibiotic complex]]
| + | |
| Structural highlights
2mc0 is a 2 chain structure with sequence from Streptomyces actuosus and Streptomyces lividans. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
TIPA_STRLI Transcriptional activator. Is activated when bound to the antibiotic thiostrepton.
Publication Abstract from PubMed
TipA is a transcriptional regulator found in diverse bacteria. It constitutes a minimal autoregulated multidrug resistance system against numerous thiopeptide antibiotics. Here we report the structures of its drug-binding domain TipAS in complexes with promothiocin A and nosiheptide, and a model of the thiostrepton complex. Drug binding induces a large transition from a partially unfolded to a globin-like structure. The structures rationalize the mechanism of promiscuous, yet specific, drug recognition: (i) a four-ring motif present in all known TipA-inducing antibiotics is recognized specifically by conserved TipAS amino acids; and (ii) the variable part of the antibiotic is accommodated within a flexible cleft that rigidifies upon drug binding. Remarkably, the identified four-ring motif is also the major interacting part of the antibiotic with the ribosome. Hence the TipA multidrug resistance mechanism is directed against the same chemical motif that inhibits protein synthesis. The observed identity of chemical motifs responsible for antibiotic function and resistance may be a general principle and could help to better define new leads for antibiotics.
Structural basis and dynamics of multidrug recognition in a minimal bacterial multidrug resistance system.,Habazettl J, Allan M, Jensen PR, Sass HJ, Thompson CJ, Grzesiek S Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5498-507. doi:, 10.1073/pnas.1412070111. Epub 2014 Dec 8. PMID:25489067[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Habazettl J, Allan M, Jensen PR, Sass HJ, Thompson CJ, Grzesiek S. Structural basis and dynamics of multidrug recognition in a minimal bacterial multidrug resistance system. Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5498-507. doi:, 10.1073/pnas.1412070111. Epub 2014 Dec 8. PMID:25489067 doi:http://dx.doi.org/10.1073/pnas.1412070111
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