Insights into Structural and Dynamical Changes Experienced by Human RNase 6 upon Ligand Binding

Narayanan, Chitra, Bernard, David N., Létourneau, Myriam, Gagnon, Jacinthe, Gagné, Donald, Bafna, Khushboo, Calmettes, Charles, Couture, Jean-François, Agarwal, Pratul K et Doucet, Nicolas ORCID: https://orcid.org/0000-0002-1952-9380 (2020). Insights into Structural and Dynamical Changes Experienced by Human RNase 6 upon Ligand Binding Biochemistry , vol. 59 , nº 6. p. 755-765. DOI: 10.1021/acs.biochem.9b00888.

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Résumé

Ribonuclease 6 (RNase 6) is one of eight catalytically active human pancreatic-type RNases that belong to a superfamily of rapidly evolving enzymes. Like some of its human homologues, RNase 6 exhibits host defense properties such as antiviral and antibacterial activities. Recently solved crystal structures of this enzyme in its nucleotide-free form show the conservation of the prototypical kidney-shaped fold preserved among vertebrate RNases, in addition to revealing the presence of a unique secondary active site. In this study, we determine the structural and conformational properties experienced by RNase 6 upon binding to substrate and product analogues. We present the first crystal structures of RNase 6 bound to a nucleotide ligand (adenosine S'-monophosphate), in addition to RNase 6 bound to phosphate ions. While the enzyme preserves B-2 subsite ligand preferences, our results show a lack of typical B-2 subsite interactions normally observed in homologous ligand-bound RNases. A comparison of the dynamical properties of RNase 6 in its apo-, substrate-, and product-bound states highlight the unique dynamical properties experienced on time scales ranging from nano- to milliseconds. Overall, our results confirm the specific evolutionary adaptation of RNase 6 relative to its unique catalytic and biological activities.

Type de document:	Article
Mots-clés libres:	Ribonuclease 6; RNase K6; nuclear magnetic resonance; conformational exchange; Carr-PurcellMeiboom-Gill; computational simulation; crystal structure; ligand binding
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	20 juill. 2021 04:18
Dernière modification:	15 févr. 2022 15:35
URI:	https://espace.inrs.ca/id/eprint/11646

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