Background: It remains unclear whether structural homologues rely on similar concerted motions to promote enzyme function. Results: Ribonuclease homologues display similar, contiguous clustering motions that can be modulated by mutagenesis. Conclusion: Conformational flexibility can be conserved between distant structural homologues. Significance: Controlling dynamics to modulate function has broad implications in protein engineering and allosteric drug design.
Eight active canonical members of the pancreatic-like ribonuclease A (RNase A) superfamily have been identified in human. All structural homologs share similar RNA-degrading functions, while also cumulating other various biological activities in different tissues. The functional homologs eosinophil-derived neurotoxin (EDN, or RNase 2) and eosinophil cationic protein (ECP, or RNase 3) are known to be expressed and secreted by eosinophils in response to infection, and have thus been postulated to play an important role in host defense and inflammatory response. We recently initiated the biophysical and dynamical investigation of several vertebrate RNase homologs and observed that clustering residue dynamics appear to be linked with the phylogeny and biological specificity of several members. Here we report the 1H, 13C and 15N backbone resonance assignments of human EDN (RNase 2) and its molecular dynamics simulation on the microsecond timescale, providing means to pursue this comparative atomic-scale functional and dynamical analysis by NMR and computation over multiple time frames.
After publication of this article, the authors noticed that a N-C dimension error was unwillingly coded in the 3D NMR spectrum "fid.com" processing script used to perform backbone assignments for this enzyme. The authors noticed that some OBS, CAR and LAB values in the "fid.com" had been switched in the y and z dimensions, probably resulting from a wrong NMRPipe selection when reading the Varian NMR experimental parameters. They have carefully re-processed, re-analyzed, re-assigned, in addition to checking all scripts to evaluate the extent of this processing error on the published assignments. Authors determined that the "fid.com" error resulted in a significant number of incorrect backbone resonance assignments, requiring us to issue corrections in Figs. 2, 3 and 4 of this published manuscript, in addition to Table S1. New versions of these figures and table are provided below. The corresponding BMRB entry has also been revised. The authors note that these modifications do not change the global message, conclusions, and molecular dynamics simulations presented in this article. The authors are grateful to David N. Bernard (INRS) for help with finding and correcting these errors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.