%0 Journal Article
%T Mechanistic insight into the catalytic activity of ββα-metallonucleases from computer simulations: Vibrio vulnificus periplasmic nuclease as a test case.
%A Bueren-Calabuig JA
%A Coderch C
%A Rico E
%A Jiménez-Ruiz A
%A Gago F
%J Chembiochem
%V 12
%N 17
%D Nov 2011 25
%M 22114054
%F 3.461
%R 10.1002/cbic.201100485
%X Using information from wild-type and mutant Vibrio vulnificus nuclease (Vvn) and I-PpoI homing endonuclease co-crystallized with different oligodeoxynucleotides, we have built the complex of Vvn with a DNA octamer and carried out a series of simulations to dissect the catalytic mechanism of this metallonuclease in a stepwise fashion. The distinct roles played in the reaction by individual active site residues, the metal cation and water molecules have been clarified by using a combination of classical molecular dynamics simulations and quantum mechanical calculations. Our results strongly support the most parsimonious catalytic mechanism, namely one in which a single water molecule from bulk solvent is used to cleave the phosphodiester bond and protonate the 3'-hydroxylate leaving group.