Insights into structural and dynamical changes experienced by human RNase 6 upon ligand binding

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 homologs, 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 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 analogs. 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 B2 subsite ligand preferences, our results show lack of typical B2 subsite interactions normally observed in homologous ligand-bound RNases. Comparison of the dynamical propertie...