biostudies-literatureToth ZSGovernment of HungaryEuropean Molecular Biology OrganizationNovo Nordisk FoundationCarlsberg FoundationNational Research, Development and Innovation Office of HungaryNovo Nordisk Fonden27171https://www.ebi.ac.uk/biostudies/studies/S-EPMC11544220biostudies-literatureUnknown14(1)The dUTPase is a key DNA repair enzyme in Mycobacterium tuberculosis, and it may serve as a novel promising anti-tuberculosis target. Stl repressor from Staphylococcus aureus was shown to bind to and inhibit dUTPases from various sources, and its expression in mycobacterial cells interfered with cell growth. To fine-tune and optimize Stl-induced inhibition of mycobacterial dUTPase, we aimed to decipher the molecular details of this interaction. Structural background of the complex between dUTPase and a truncated Stl lacking the repressor C-terminal homodimerization domain has been described, however, the effects of this truncation of Stl on enzyme binding and inhibition are still not known. Using several independent biophysical, structural and enzyme kinetic methods, here we show that lackScientific reportsThe homodimerization domain of the Stl repressor is crucial for efficient inhibition of mycobacterial dUTPase.PMC11544220K135231NNF22OC0073736K146890VEKOP-2.3.2-16-2017-00014ALTF 336-2021CF20-04122018-1.2.1-NKP-2018-00005Miller RLJaroentomeechai TBenedek AOzohanics OLeveles IHarmat VToth ZSNyiri KNagy GNVertessy BGAlvarez MBfalseThe homodimerization domain of the Stl repressor is crucial for efficient inhibition of mycobacterial dUTPase.The dUTPase is a key DNA repair enzyme in Mycobacterium tuberculosis, and it may serve as a novel promising anti-tuberculosis target. Stl repressor from Staphylococcus aureus was shown to bind to and inhibit dUTPases from various sources, and its expression in mycobacterial cells interfered with cell growth. To fine-tune and optimize Stl-induced inhibition of mycobacterial dUTPase, we aimed to decipher the molecular details of this interaction. Structural background of the complex between dUTPase and a truncated Stl lacking the repressor C-terminal homodimerization domain has been described, however, the effects of this truncation of Stl on enzyme binding and inhibition are still not known. Using several independent biophysical, structural and enzyme kinetic methods, here we show that lack2024-01-01T00:00:00Z2024 Nov2026-06-03T00:51:30.662Z2025-04-19T17:27:35.037ZS-EPMC115442203951124210.1038/s41598-024-76349-2