|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of MAB_4384 tetR== | | ==Crystal structure of MAB_4384 tetR== |
| - | <StructureSection load='5ovy' size='340' side='right' caption='[[5ovy]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='5ovy' size='340' side='right'caption='[[5ovy]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ovy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myca9 Myca9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OVY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OVY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ovy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacteroides_abscessus_ATCC_19977 Mycobacteroides abscessus ATCC 19977]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OVY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OVY FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAB_4384 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=561007 MYCA9])</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]] 1.9Å</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=5ovy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ovy OCA], [http://pdbe.org/5ovy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ovy RCSB], [http://www.ebi.ac.uk/pdbsum/5ovy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ovy 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=5ovy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ovy OCA], [https://pdbe.org/5ovy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ovy RCSB], [https://www.ebi.ac.uk/pdbsum/5ovy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ovy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/B1MJU8_MYCA9 B1MJU8_MYCA9] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 20: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Myca9]] | + | [[Category: Large Structures]] |
| - | [[Category: Blaise, M]] | + | [[Category: Mycobacteroides abscessus ATCC 19977]] |
| - | [[Category: Ghigo, E]] | + | [[Category: Blaise M]] |
| - | [[Category: Gutierrez, A V]] | + | [[Category: Ghigo E]] |
| - | [[Category: Kremer, L]] | + | [[Category: Gutierrez AV]] |
| - | [[Category: Richard, M]] | + | [[Category: Kremer L]] |
| - | [[Category: Viljoen, A]] | + | [[Category: Richard M]] |
| - | [[Category: Antibiotic resistance]]
| + | [[Category: Viljoen A]] |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Efflux pump regulation]]
| + | |
| - | [[Category: Tetr]]
| + | |
| Structural highlights
Function
B1MJU8_MYCA9
Publication Abstract from PubMed
Mycobacterium abscessus is an emerging human pathogen causing severe pulmonary infections and is refractory to standard antibiotherapy, yet few drug resistance mechanisms have been reported in this organism. Recently, mutations in MAB_4384 leading to up-regulation of the MmpS5/MmpL5 efflux pump were linked to increased resistance to thiacetazone derivatives. Herein, the DNA-binding activity of MAB_4384 was investigated by electrophoretic mobility shift assays using the palindromic sequence IRS5/L5 located upstream of mmpS5/mmpL5. Introduction of point mutations within IRS5/L5 identified the sequence requirements for optimal binding of the regulator. Moreover, formation of the protein/IRS5/L5 complex was severely impaired for MAB_4384 harboring D14N or F57L substitutions. IRS5/L5/lacZ reporter fusions in M. abscessus demonstrated increased beta-galactosidase activity either in strains lacking a functional MAB_4384 or in cultures treated with the TAC analogs. In addition, X-ray crystallography confirmed a typical TetR homodimeric structure of MAB_4384 and unraveled a putative ligand binding site in which the analogs could be docked. Overall, these results support drug recognition of the MAB_4384 TetR regulator, alleviating its binding to IRS5/L5 and steering up-regulation of MmpS5/MmpL5. This study provides new mechanistic and structural details of TetR-dependent regulatory mechanisms of efflux pumps and drug resistance in mycobacteria.
Mechanistic and Structural Insights Into the Unique TetR-Dependent Regulation of a Drug Efflux Pump in Mycobacterium abscessus.,Richard M, Gutierrez AV, Viljoen AJ, Ghigo E, Blaise M, Kremer L Front Microbiol. 2018 Apr 5;9:649. doi: 10.3389/fmicb.2018.00649. eCollection, 2018. PMID:29675007[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Richard M, Gutierrez AV, Viljoen AJ, Ghigo E, Blaise M, Kremer L. Mechanistic and Structural Insights Into the Unique TetR-Dependent Regulation of a Drug Efflux Pump in Mycobacterium abscessus. Front Microbiol. 2018 Apr 5;9:649. doi: 10.3389/fmicb.2018.00649. eCollection, 2018. PMID:29675007 doi:http://dx.doi.org/10.3389/fmicb.2018.00649
|
