6ZWT

Crystal structure of DNA-binding domain of OmpR of two-component system of Acinetobacter baumannii

Summary for 6ZWT

• Entry DOI: 10.2210/pdb6zwt/pdb
• Descriptor: Two-component response regulator, SULFATE ION, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• Functional Keywords: dna binding protein, ompr of a. baumannii, two-component system
• Biological source: Acinetobacter baumannii (strain SDF)
• Total number of polymer chains: 4
• Total formula weight: 53030.13

Authors

Narwal, M.,Lucchini, V.,Trebosc, V.,Gartenmann, S.,Pieren, M.,Kemmer, C.,Kammerer, R.A. (deposition date: 2020-07-28, release date: 2021-08-11, Last modification date: 2024-02-07)

Primary citation

Trebosc, V.,Lucchini, V.,Narwal, M.,Wicki, B.,Gartenmann, S.,Schellhorn, B.,Schill, J.,Bourotte, M.,Frey, D.,Grunberg, J.,Trauner, A.,Ferrari, L.,Felici, A.,Champion, O.L.,Gitzinger, M.,Lociuro, S.,Kammerer, R.A.,Kemmer, C.,Pieren, M.
Targeting virulence regulation to disarm Acinetobacter baumannii pathogenesis.
Virulence, 13:1868-1883, 2022

PubMed Abstract: The development of anti-virulence drug therapy against infections would provide an alternative to traditional antibacterial therapy that are increasingly failing. Here, we demonstrate that the OmpR transcriptional regulator plays a pivotal role in the pathogenesis of diverse clinical strains in multiple murine and invertebrate infection models. We identified OmpR-regulated genes using RNA sequencing and further validated two genes whose expression can be used as robust biomarker to quantify OmpR inhibition in . Moreover, the determination of the structure of the OmpR DNA binding domain of and the development of protein-DNA binding assays enabled the identification of an OmpR small molecule inhibitor. We conclude that OmpR is a valid and unexplored target to fight infections and we believe that the described platform combining methods, OmpR inhibitory assays and surrogate infection model will facilitate future drug discovery programs.

PubMed: 36261919
DOI: 10.1080/21505594.2022.2135273

Experimental method

X-RAY DIFFRACTION (2.2 Å)