Matches in SemOpenAlex for { <https://semopenalex.org/work/W2807563188> ?p ?o ?g. }
- W2807563188 abstract "Abstract Human deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase), essential for DNA integrity, acts as a survival factor for tumor cells and is a target for cancer chemotherapy. Here we report that the Staphylococcal repressor protein Stl SaPIBov1 (Stl) forms strong complex with human dUTPase. Functional analysis reveals that this interaction results in significant reduction of both dUTPase enzymatic activity and DNA binding capability of Stl. We conducted structural studies to understand the mechanism of this mutual inhibition. Small-angle X-ray scattering (SAXS) complemented with hydrogen-deuterium exchange mass spectrometry (HDX-MS) data allowed us to obtain 3D structural models comprising a trimeric dUTPase complexed with separate Stl monomers. These models thus reveal that upon dUTPase-Stl complex formation the functional homodimer of Stl repressor dissociates, which abolishes the DNA binding ability of the protein. Active site forming dUTPase segments were directly identified to be involved in the dUTPase-Stl interaction by HDX-MS, explaining the loss of dUTPase activity upon complexation. Our results provide key novel structural insights that pave the way for further applications of the first potent proteinaceous inhibitor of human dUTPase." @default.
- W2807563188 created "2018-06-13" @default.
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- W2807563188 date "2018-03-12" @default.
- W2807563188 modified "2023-10-16" @default.
- W2807563188 title "Structural model of human dUTPase in complex with a novel proteinaceous inhibitor" @default.
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- W2807563188 doi "https://doi.org/10.1038/s41598-018-22145-8" @default.
- W2807563188 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5847570" @default.