Subtle functional collective motions in pancreatic-like ribonucleases: From ribonuclease a to angiogenin.

The anal. of the dynamic behavior of enzymes is fundamental to structural biol. A direct relationship between protein flexibility and biol. function has been shown for bovine pancreatic RNase (RNase A) (Rasmussen et al., Nature 1992;357:423-424). More recently, crystallog. studies have shown that functional motions in RNase A involve the enzyme b-sheet regions that move concertedly on substrate binding and release (Vitagliano et al., Proteins 2002;46:97-104). These motions have been shown to correspond to intrinsic dynamic properties of the native enzyme by mol. dynamics (MD) simulations. To unveil the occurrence of these collective motions in other members of pancreatic-like superfamily, we carried out MD simulations on human angiogenin (Ang). Essential dynamics (ED) analyses performed on the trajectories reveal that Ang exhibits collective motions similar to RNase A, despite the limited sequence identity (33%) of the two proteins. Furthermore, we show that these collective motions are also present in ensembles of exptl. detd. structures of both Ang and RNase A. Finally, these subtle concerted b-sheet motions were also obsd. for other two members of the pancreatic-like superfamily by comparing the ligand-bound and ligand-free structures of these enzymes. Taken together, these findings suggest that pancreatic-like RNases share an evolutionary conserved dynamic behavior consisting of subtle b-sheet motions, which are essential for substrate binding and release.