View source for 2mbz


==Structural Basis of a Thiopeptide Antibiotic Multidrug Resistance System from Streptomyces lividans:Promothiocin A in Complex with TipAS==
<StructureSection load='2mbz' size='340' side='right'caption='[[2mbz]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2mbz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_lividans Streptomyces lividans] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MBZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BB9:(2Z)-2-AMINO-3-SULFANYLPROP-2-ENOIC+ACID'>BB9</scene>, <scene name='pdbligand=MOZ:(2Z)-2-AMINO-3-HYDROXYBUT-2-ENOIC+ACID'>MOZ</scene>, <scene name='pdbligand=NAK:AMINO-ACRYLATE'>NAK</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=2mbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mbz OCA], [https://pdbe.org/2mbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mbz RCSB], [https://www.ebi.ac.uk/pdbsum/2mbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mbz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TIPA_STRLI TIPA_STRLI] Transcriptional activator. Is activated when bound to the antibiotic thiostrepton.
<div style="background-color:#fffaf0;">
== 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<ref>PMID:25489067</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2mbz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces lividans]]
[[Category: Synthetic construct]]
[[Category: Allan MG]]
[[Category: Grzesiek S]]
[[Category: Habazettl J]]
[[Category: Jensen P]]
[[Category: Sass H]]