5HSO

Crystal structure of MYCOBACTERIUM TUBERCULOSIS MARR FAMILY PROTEIN Rv2887 complex with DNA

5HSO の概要

• エントリーDOI: 10.2210/pdb5hso/pdb
• 関連するPDBエントリー: 5HSL 5HSM 5HSN
• 分子名称: Uncharacterized HTH-type transcriptional regulator Rv2887, DNA (30-MER), the upstream sequence of Rv0560c (3 entities in total)
• 機能のキーワード: hth-type transcriptional regulator, dna binding, salicylic acid binding, transcription
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 86502.48

構造登録者

Gao, Y.R.,Li, D.F.,Wang, D.C.,Bi, L.J. (登録日: 2016-01-26, 公開日: 2017-02-01, 最終更新日: 2024-03-20)

主引用文献

Gao, Y.R.,Li, D.F.,Fleming, J.,Zhou, Y.F.,Liu, Y.,Deng, J.Y.,Zhou, L.,Zhou, J.,Zhu, G.F.,Zhang, X.E.,Wang, D.C.,Bi, L.J.
Structural analysis of the regulatory mechanism of MarR protein Rv2887 in M. tuberculosis
Sci Rep, 7:6471-6471, 2017

PubMed Abstract: MarR family proteins are transcriptional regulators that control expression of bacterial proteins involved in metabolism, virulence, stress responses and multi-drug resistance, mainly via ligand-mediated attenuation of DNA binding. Greater understanding of their underlying regulatory mechanism may open up new avenues for the effective treatment of bacterial infections. To gain molecular insight into the mechanism of Rv2887, a MarR family protein in M. tuberculosis, we first showed that it binds salicylate (SA) and para-aminosalicylic acid (PAS), its structural analogue and an antitubercular drug, in a 1:1 stoichiometry with high affinity. Subsequent determination and analysis of Rv2887 crystal structures in apo form, and in complex with SA, PAS and DNA showed that SA and PAS bind to Rv2887 at similar sites, and that Rv2887 interacts with DNA mainly by insertion of helix α4 into the major groove. Ligand binding triggers rotation of the wHTH domain of Rv2887 toward the dimerization domain, causing changes in protein conformation such that it can no longer bind to a 27 bp recognition sequence in the upstream region of gene Rv0560c. The structures provided here lay a foundation for the design of small molecules that target Rv2887, a potential new approach for the development of anti-mycobacterials.

PubMed: 28743871
DOI: 10.1038/s41598-017-01705-4

実験手法

X-RAY DIFFRACTION (2.5 Å)