6N8A

Crystal structure of selenomethionine-containing AcaB from uropathogenic E. coli

Summary for 6N8A

• Entry DOI: 10.2210/pdb6n8a/pdb
• Descriptor: transcription regulator AcaB, CHLORIDE ION (3 entities in total)
• Functional Keywords: uropathogenic e. coli; new-delhi metallo-beta-lactamase; ndm; a/c plasmid; acab; transcription regulation, transcription
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 44204.04

Authors

Luo, Z.,Hancock, S.J.,Schembri, M.A.,Kobe, B. (deposition date: 2018-11-28, release date: 2020-07-15, Last modification date: 2024-11-13)

Primary citation

Hancock, S.J.,Phan, M.D.,Luo, Z.,Lo, A.W.,Peters, K.M.,Nhu, N.T.K.,Forde, B.M.,Whitfield, J.,Yang, J.,Strugnell, R.A.,Paterson, D.L.,Walsh, T.R.,Kobe, B.,Beatson, S.A.,Schembri, M.A.
Comprehensive analysis of IncC plasmid conjugation identifies a crucial role for the transcriptional regulator AcaB.
Nat Microbiol, 5:1340-1348, 2020

PubMed Abstract: The IncC family of broad-host-range plasmids enables the spread of antibiotic resistance genes among human enteric pathogens. Although aspects of IncC plasmid conjugation have been well studied, many roles of conjugation genes have been assigned based solely on sequence similarity. We applied hypersaturated transposon mutagenesis and transposon-directed insertion-site sequencing to determine the set of genes required for IncC conjugation. We identified 27 conjugation genes, comprising 19 that were previously identified (including two regulatory genes, acaDC) and eight not previously associated with conjugation. We show that one previously unknown gene, acaB, encodes a transcriptional regulator that has a crucial role in the regulation of IncC conjugation. AcaB binds upstream of the acaDC promoter to increase acaDC transcription; in turn, AcaDC activates the transcription of IncC conjugation genes. We solved the crystal structure of AcaB at 2.9-Å resolution and used this to guide functional analyses that reveal how AcaB binds to DNA. This improved understanding of IncC conjugation provides a basis for the development of new approaches to reduce the spread of these multi-drug-resistance plasmids.

PubMed: 32807890
DOI: 10.1038/s41564-020-0775-0

Experimental method

X-RAY DIFFRACTION (3.4011 Å)