7M0S

N-terminal domain of PmrA from Acinetobacter baumannii

7M0S の概要

• エントリーDOI: 10.2210/pdb7m0s/pdb
• 分子名称: Two-component system response regulator PmrA (2 entities in total)
• 機能のキーワード: colistin resistance, transcription
• 由来する生物種: Acinetobacter baumannii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28849.37

構造登録者

Palethorpe, S.,Milton, M.E.,Cavanagh, J. (登録日: 2021-03-11, 公開日: 2021-11-03, 最終更新日: 2023-10-18)

主引用文献

Palethorpe, S.,Milton, M.E.,Pesci, E.C.,Cavanagh, J.
Structure of the Acinetobacter baumannii PmrA receiver domain and insights into clinical mutants affecting DNA binding and promoting colistin resistance.
J.Biochem., 170:787-800, 2022

PubMed Abstract: Acinetobacter baumannii is an insidious emerging nosocomial pathogen that has developed resistance to all available antimicrobials, including the last resort antibiotic, colistin. Colistin resistance often occurs due to mutations in the PmrAB two-component regulatory system. To better understand the regulatory mechanisms contributing to colistin resistance, we have biochemically characterized the A. baumannii PmrA response regulator. Initial DNA-binding analysis shows that A. baumannii PmrA bound to the Klebsiella pneumoniae PmrA box motif. This prompted analysis of the putative A. baumannii PmrAB regulon that indicated that the A. baumannii PmrA consensus box is 5'-HTTAAD N5 HTTAAD. Additionally, we provide the first structural information for the A. baumannii PmrA N-terminal domain through X-ray crystallography and we present a full-length model using molecular modelling. From these studies, we were able to infer the effects of two critical PmrA mutations, PmrA::I13M and PmrA::P102R, both of which confer increased colistin resistance. Based on these data, we suggest structural and dynamic reasons for how these mutations can affect PmrA function and hence encourage resistive traits. Understanding these mechanisms will aid in the development of new targeted antimicrobial therapies. Graphical Abstract.

PubMed: 34585233
DOI: 10.1093/jb/mvab102

実験手法

X-RAY DIFFRACTION (1.64 Å)