7JNP

MtrR bound to the rpoH operator from Neisseria gonorrhoeae

7JNP の概要

• エントリーDOI: 10.2210/pdb7jnp/pdb
• 分子名称: HTH-type transcriptional regulator MtrR, DNA (5'-D(*TP*TP*AP*CP*AP*TP*AP*CP*AP*AP*CP*CP*AP*CP*GP*TP*AP*TP*GP*TP*A)-3'), DNA (5'-D(*TP*AP*CP*AP*TP*AP*CP*GP*TP*GP*GP*TP*TP*GP*TP*AP*TP*GP*TP*AP*A)-3'), ... (5 entities in total)
• 機能のキーワード: tetr family, transcription regulator, helix-turn-helix motif, dna binding protein
• 由来する生物種: Neisseria gonorrhoeae; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 62207.00

構造登録者

Beggs, G.A.,Shafer, W.M.,Brennan, R.G. (登録日: 2020-08-05, 公開日: 2021-03-24, 最終更新日: 2023-10-18)

主引用文献

Beggs, G.A.,Ayala, J.C.,Kavanaugh, L.G.,Read, T.D.,Hooks, G.M.,Schumacher, M.A.,Shafer, W.M.,Brennan, R.G.
Structures of Neisseria gonorrhoeae MtrR-operator complexes reveal molecular mechanisms of DNA recognition and antibiotic resistance-conferring clinical mutations.
Nucleic Acids Res., 49:4155-4170, 2021

PubMed Abstract: Mutations within the mtrR gene are commonly found amongst multidrug resistant clinical isolates of Neisseria gonorrhoeae, which has been labelled a superbug by the Centers for Disease Control and Prevention. These mutations appear to contribute to antibiotic resistance by interfering with the ability of MtrR to bind to and repress expression of its target genes, which include the mtrCDE multidrug efflux transporter genes and the rpoH oxidative stress response sigma factor gene. However, the DNA-recognition mechanism of MtrR and the consensus sequence within these operators to which MtrR binds has remained unknown. In this work, we report the crystal structures of MtrR bound to the mtrCDE and rpoH operators, which reveal a conserved, but degenerate, DNA consensus binding site 5'-MCRTRCRN4YGYAYGK-3'. We complement our structural data with a comprehensive mutational analysis of key MtrR-DNA contacts to reveal their importance for MtrR-DNA binding both in vitro and in vivo. Furthermore, we model and generate common clinical mutations of MtrR to provide plausible biochemical explanations for the contribution of these mutations to multidrug resistance in N. gonorrhoeae. Collectively, our findings unveil key biological mechanisms underlying the global stress responses of N. gonorrhoeae.

PubMed: 33784401
DOI: 10.1093/nar/gkab213

実験手法

X-RAY DIFFRACTION (2.6 Å)