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- W2025696525 startingPage "e46804" @default.
- W2025696525 abstract "Bovine seminal (BS) RNase, the unique natively dimeric member of the RNase super-family, represents a special case not only for its additional biological actions but also for the singular features of 3D domain swapping. The native enzyme is indeed a mixture of two isoforms: M = M, a dimer held together by two inter-subunit disulfide bonds, and MxM, 70% of the total, which, besides the two mentioned disulfides, is additionally stabilized by the swapping of its N-termini. When lyophilized from 40% acetic acid, BS-RNase oligomerizes as the super-family proto-type RNase A does. In this paper, we induced BS-RNase self-association and analyzed the multimers by size-exclusion chromatography, cross-linking, electrophoresis, mutagenesis, dynamic light scattering, molecular modelling. Finally, we evaluated their enzymatic and cytotoxic activities. Several BS-RNase domain-swapped oligomers were detected, including two tetramers, one exchanging only the N-termini, the other being either N- or C-swapped. The C-swapping event, confirmed by results on a BS-K113N mutant, has been firstly seen in BS-RNase here, and probably stabilizes also multimers larger than tetramers. Interestingly, all BS-RNase oligomers are more enzymatically active than the native dimer and, above all, they display a cytotoxic activity that definitely increases with the molecular weight of the multimers. This latter feature, to date unknown for BS-RNase, suggests again that the self-association of RNases strongly modulates their biological and potentially therapeutic properties." @default.
- W2025696525 created "2016-06-24" @default.
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- W2025696525 creator A5091081243 @default.
- W2025696525 date "2012-10-11" @default.
- W2025696525 modified "2023-10-18" @default.
- W2025696525 title "Double Domain Swapping in Bovine Seminal RNase: Formation of Distinct N- and C-swapped Tetramers and Multimers with Increasing Biological Activities" @default.
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- W2025696525 doi "https://doi.org/10.1371/journal.pone.0046804" @default.
- W2025696525 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3469567" @default.
- W2025696525 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23071641" @default.
- W2025696525 hasPublicationYear "2012" @default.
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