7M0S

N-terminal domain of PmrA from Acinetobacter baumannii

Summary for 7M0S

• Entry DOI: 10.2210/pdb7m0s/pdb
• Descriptor: Two-component system response regulator PmrA (2 entities in total)
• Functional Keywords: colistin resistance, transcription
• Biological source: Acinetobacter baumannii
• Total number of polymer chains: 2
• Total formula weight: 28849.37

Authors

Palethorpe, S.,Milton, M.E.,Cavanagh, J. (deposition date: 2021-03-11, release date: 2021-11-03, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.64 Å)