5OVY
Crystal structure of MAB_4384 tetR
Summary for 5OVY
| Entry DOI | 10.2210/pdb5ovy/pdb |
| Descriptor | Putative transcriptional regulator, TetR family (2 entities in total) |
| Functional Keywords | tetr, efflux pump regulation, antibiotic resistance, dna binding protein |
| Biological source | Mycobacterium abscessus (strain ATCC 19977 / DSM 44196 / CIP 104536 / JCM 13569 / NCTC 13031 / TMC 1543) |
| Total number of polymer chains | 2 |
| Total formula weight | 49559.79 |
| Authors | Richard, M.,Gutierrez, A.V.,Viljoen, A.,Ghigo, E.,Blaise, M.,Kremer, L. (deposition date: 2017-08-30, release date: 2018-03-28, Last modification date: 2024-05-08) |
| Primary citation | Richard, M.,Gutierrez, A.V.,Viljoen, A.J.,Ghigo, E.,Blaise, M.,Kremer, L. Mechanistic and Structural Insights Into the Unique TetR-Dependent Regulation of a Drug Efflux Pump inMycobacterium abscessus. Front Microbiol, 9:649-649, 2018 Cited by PubMed Abstract: 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 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 IR located upstream of . Introduction of point mutations within IR identified the sequence requirements for optimal binding of the regulator. Moreover, formation of the protein/IR complex was severely impaired for MAB_4384 harboring D14N or F57L substitutions. IR reporter fusions in demonstrated increased β-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 IR 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. PubMed: 29675007DOI: 10.3389/fmicb.2018.00649 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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