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Structural mechanism for regulation of DNA binding of BpsR, a Bordetella regulator of biofilm formation, by 6-hydroxynicotinic acid


Autoři: William T. Booth aff001;  Ryan R. Davis aff001;  Rajendar Deora aff002;  Thomas Hollis aff001
Působiště autorů: Department of Biochemistry, Center for Structural Biology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America aff001;  Department of Microbial Infection and Immunity, and Department of Microbiology, The Ohio State University, Columbus, Ohio, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223387

Souhrn

Bordetella bacteria are respiratory pathogens of humans, birds, and livestock. Bordetella pertussis the causative agent of whopping cough remains a significant health issue. The transcriptional regulator, BpsR, represses a number of Bordetella genes relating to virulence, cell adhesion, cell motility, and nicotinic acid metabolism. DNA binding of BpsR is allosterically regulated by interaction with 6-hydroxynicotinic acid (6HNA), the first product in the nicotinic acid degradation pathway. To understand the mechanism of this regulation, we have determined the crystal structures of BpsR and BpsR in complex with 6HNA. The structures reveal that BpsR binding of 6HNA induces a conformational change in the protein to prevent DNA binding. We have also identified homologs of BpsR in other Gram negative bacteria in which the amino acids involved in recognition of 6HNA are conserved, suggesting a similar mechanism for regulating nicotinic acid degradation.

Klíčová slova:

Crystal structure – Dimers – DNA structure – DNA-binding proteins – Monomers – Protein structure – Bordetella – Bordetella pertussis


Zdroje

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