7cla
From Proteopedia
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<StructureSection load='7cla' size='340' side='right'caption='[[7cla]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='7cla' size='340' side='right'caption='[[7cla]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[7cla]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[7cla]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Caulobacter_vibrioides_CB15 Caulobacter vibrioides CB15]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CLA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CLA FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7cla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cla OCA], [https://pdbe.org/7cla PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cla RCSB], [https://www.ebi.ac.uk/pdbsum/7cla PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cla ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/SKGA_CAUVC SKGA_CAUVC] Regulates the induction of katG (catalase-peroxidase) in stationary phase. |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| - | Investigations of bacterial resistance strategies can aid in the development of new antimicrobial drugs as a countermeasure to the increasing worldwide prevalence of bacterial antibiotic resistance. One such strategy involves the TipA class of transcription factors, which constitute minimal autoregulated multidrug resistance (MDR) systems against diverse antibiotics. However, we have insufficient information regarding how antibiotic binding induces transcriptional activation to design molecules that could interfere with this process. To learn more, we determined the crystal structure of SkgA from Caulobacter crescentus as a representative TipA protein. We identified an unexpected spatial orientation and location of the antibiotic binding TipAS effector domain in the apo state. We observed that the alpha6-alpha7 region of the TipAS domain, which is canonically responsible for forming the lid of antibiotic binding cleft to tightly enclose the bound antibiotic, is involved in the dimeric interface and stabilized via interaction with the DNA-binding domain in the apo state. Further structural and biochemical analyses demonstrated that the unliganded TipAS domain sterically hinders promoter DNA binding | + | Investigations of bacterial resistance strategies can aid in the development of new antimicrobial drugs as a countermeasure to the increasing worldwide prevalence of bacterial antibiotic resistance. One such strategy involves the TipA class of transcription factors, which constitute minimal autoregulated multidrug resistance (MDR) systems against diverse antibiotics. However, we have insufficient information regarding how antibiotic binding induces transcriptional activation to design molecules that could interfere with this process. To learn more, we determined the crystal structure of SkgA from Caulobacter crescentus as a representative TipA protein. We identified an unexpected spatial orientation and location of the antibiotic-binding TipAS effector domain in the apo state. We observed that the alpha6-alpha7 region of the TipAS domain, which is canonically responsible for forming the lid of antibiotic-binding cleft to tightly enclose the bound antibiotic, is involved in the dimeric interface and stabilized via interaction with the DNA-binding domain in the apo state. Further structural and biochemical analyses demonstrated that the unliganded TipAS domain sterically hinders promoter DNA binding but undergoes a remarkable conformational shift upon antibiotic binding to release this autoinhibition via a switch of its alpha6-alpha7 region. Hence, the promoters for MDR genes including tipA and RNA polymerases become available for transcription, enabling efficient antibiotic resistance. These insights into the molecular mechanism of activation of TipA proteins advance our understanding of TipA proteins, as well as bacterial MDR systems, and may provide important clues to block bacterial resistance. |
| - | Antibiotic binding releases autoinhibition of the TipA multidrug-resistance transcriptional regulator.,Jiang X, Zhang L, Teng M, Li X J Biol Chem. 2020 | + | Antibiotic binding releases autoinhibition of the TipA multidrug-resistance transcriptional regulator.,Jiang X, Zhang L, Teng M, Li X J Biol Chem. 2020 Dec 18;295(51):17865-17876. doi: 10.1074/jbc.RA120.016295. PMID:33454020<ref>PMID:33454020</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7cla" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7cla" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Tetracycline repressor protein 3D structures|Tetracycline repressor protein 3D structures]] | ||
| + | *[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Caulobacter vibrioides CB15]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Jiang | + | [[Category: Jiang X]] |
| - | [[Category: Li | + | [[Category: Li X]] |
| - | [[Category: Teng | + | [[Category: Teng M]] |
| - | [[Category: Zhang | + | [[Category: Zhang L]] |
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Current revision
Crystal structure of HTH-type transcriptional regulator SkgA from Caulobacter crescentus
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