{"entity": "researcher", "timestamp": "2026-08-25T13:20:24.595Z", "family": "Bello-Madruga", "given": "Roberto", "initials": "R", "orcid": "0009-0003-8474-3951", "affiliations": ["Department of Biochemistry and Molecular Biology, Universitat Aut\u00f2noma de Barcelona, Cerdanyola del Vall\u00e8s, Spain."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc87326cf60e43eaaf626fa0f9c462c7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc87326cf60e43eaaf626fa0f9c462c7"}}, "publications": [{"entity": "publication", "iuid": "d64bbf17c4ef4608867e1f85efdd2335", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d64bbf17c4ef4608867e1f85efdd2335.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d64bbf17c4ef4608867e1f85efdd2335"}}, "title": "Targeting MarA N-terminal domain dynamics to prevent DNA binding.", "authors": [{"family": "Corbella", "given": "Marina", "initials": "M"}, {"family": "Moreira", "given": "C\u00e1tia", "initials": "C"}, {"family": "Bello-Madruga", "given": "Roberto", "initials": "R", "orcid": "0009-0003-8474-3951", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc87326cf60e43eaaf626fa0f9c462c7.json"}}, {"family": "Torrent Burgas", "given": "Marc", "initials": "M"}, {"family": "Kamerlin", "given": "Shina C L", "initials": "SCL", "orcid": "0000-0002-3190-1173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4540c85432f4cdf952b0ef7cfe1d875.json"}}, {"family": "Blair", "given": "Jessica M A", "initials": "JMA"}, {"family": "Sancho-Vaello", "given": "Enea", "initials": "E", "orcid": "0000-0003-1383-2001", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8abbbe0590514728ab08a9611a06afb4.json"}}], "type": "journal article", "published": "2025-01-00", "journal": {"title": "Protein Sci.", "issn": "1469-896X", "volume": "34", "issue": "1", "pages": "e5258", "issn-l": "0961-8368"}, "abstract": "Efflux is one of the mechanisms employed by Gram-negative bacteria to become resistant to routinely used antibiotics. The inhibition of efflux by targeting their regulators is a promising strategy to re-sensitize bacterial pathogens to antibiotics. AcrAB-TolC is the main resistance-nodulation-division efflux pump in Enterobacteriaceae. MarA is an AraC/XylS family global regulator that regulates more than 40 genes related to the antimicrobial resistance phenotype, including acrAB. The aim of this work was to understand the role of the N-terminal helix of MarA in the mechanism of DNA binding. An N-terminal deletion of MarA showed that the N-terminal helix is critical for recognition of the functional marboxes. By engineering two double cysteine variants of MarA that form a disulfide bond between the N-terminal helix and the hydrophobic core of one of the helices in direct DNA contact, and combining in vitro electrophoretic mobility assays, in vivo measurements of acrAB transcription using a GFP reporter system, and molecular dynamic simulations, it was shown that the immobilization of the N-terminal helix of MarA prevents binding to DNA. This inhibited conformation seems to be universal for the monomeric members of the AraC/XylS family, as suggested by additional molecular dynamics simulations of the two-domain protein Rob. These results point to the N-terminal helix of the AraC/XylS family monomeric regulators as a promising target for the development of inhibitors.", "doi": "10.1002/pro.5258", "pmid": "39660948", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11633057"}], "notes": [], "created": "2026-08-21T11:04:36.291Z", "modified": "2026-08-21T11:04:36.424Z"}]}