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

Autor: Narayanan C; Centre Armand-Frappier Santé Biotechnologie , Institut National de la Recherche Scientifique (INRS), Université du Québec , 531 Boulevard des Prairies , Laval , Quebec City H7V 1B7 , Canada., Bernard DN; Centre Armand-Frappier Santé Biotechnologie , Institut National de la Recherche Scientifique (INRS), Université du Québec , 531 Boulevard des Prairies , Laval , Quebec City H7V 1B7 , Canada., Létourneau M; Centre Armand-Frappier Santé Biotechnologie , Institut National de la Recherche Scientifique (INRS), Université du Québec , 531 Boulevard des Prairies , Laval , Quebec City H7V 1B7 , Canada., Gagnon J; Centre Armand-Frappier Santé Biotechnologie , Institut National de la Recherche Scientifique (INRS), Université du Québec , 531 Boulevard des Prairies , Laval , Quebec City H7V 1B7 , Canada., Gagné D; Centre Armand-Frappier Santé Biotechnologie , Institut National de la Recherche Scientifique (INRS), Université du Québec , 531 Boulevard des Prairies , Laval , Quebec City H7V 1B7 , Canada., Bafna K; Genome Science and Technology , University of Tennesse , Knoxville , Tennessee 37996 , United States., Calmettes C; Centre Armand-Frappier Santé Biotechnologie , Institut National de la Recherche Scientifique (INRS), Université du Québec , 531 Boulevard des Prairies , Laval , Quebec City H7V 1B7 , Canada.; PROTEO, the Québec Network for Research on Protein Function, Engineering, and Applications , Université Laval , 1045 Avenue de la Médecine , Quebec , Quebec G1V 0A6 , Canada., Couture JF; Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology , University of Ottawa , 451 Smyth Road , Ottawa , Ontario K1H 8M5 , Canada., Agarwal PK; Department of Biochemistry, Cellular and Molecular Biology , University of Tennessee , Knoxville , Tennessee 37996 , United States., Doucet N; Centre Armand-Frappier Santé Biotechnologie , Institut National de la Recherche Scientifique (INRS), Université du Québec , 531 Boulevard des Prairies , Laval , Quebec City H7V 1B7 , Canada.; PROTEO, the Québec Network for Research on Protein Function, Engineering, and Applications , Université Laval , 1045 Avenue de la Médecine , Quebec , Quebec G1V 0A6 , Canada.
Jazyk: angličtina
Zdroj: Biochemistry [Biochemistry] 2020 Feb 18; Vol. 59 (6), pp. 755-765. Date of Electronic Publication: 2020 Jan 24.
DOI: 10.1021/acs.biochem.9b00888
Abstrakt: 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 5'-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.
Databáze: MEDLINE
Externí odkaz: