Solvent Structure and Hammerhead Ribozyme Catalysis

@article{citeulike:2837075, abstract = {Summary Although the hammerhead ribozyme is regarded as a prototype for understanding RNA catalysis, the mechanistic roles of associated metal ions and water molecules in the cleavage reaction remain controversial. We have investigated the catalytic potential of observed divalent metal ions and water molecules bound to a 2 \r{A} structure of the full-length hammerhead ribozyme by using X-ray crystallography in combination with molecular dynamics simulations. A single Mn2+ is observed to bind directly to the A9 phosphate in the active site, accompanying a hydrogen-bond network involving a well-ordered water molecule spanning N1 of G12 (the general base) and 2'-O of G8 (previously implicated in general acid catalysis) that we propose, based on molecular dynamics calculations, facilitates proton transfer in the cleavage reaction. Phosphate-bridging metal interactions and other mechanistic hypotheses are also tested with this approach.}, author = {Martick, Monika and Lee, Tai-Sung and York, Darrin M. and Scott, William G. }, citeulike-article-id = {2837075}, doi = {10.1016/j.chembiol.2008.03.010}, journal = {Chemistry \& Biology}, keywords = {nucleic\_acids, solvation}, month = {April}, number = {4}, pages = {332--342}, posted-at = {2008-05-27 11:19:49}, priority = {0}, title = {Solvent Structure and Hammerhead Ribozyme Catalysis}, url = {http://dx.doi.org/10.1016/j.chembiol.2008.03.010}, volume = {15}, year = {2008} }

TY - JOUR ID - citeulike:2837075 L3 - citeulike-article-id:2837075 TI - Solvent Structure and Hammerhead Ribozyme Catalysis JF - Chemistry & Biology VL - 15 IS - 4 SP - 332 EP - 342 N2 - Summary Although the hammerhead ribozyme is regarded as a prototype for understanding RNA catalysis, the mechanistic roles of associated metal ions and water molecules in the cleavage reaction remain controversial. We have investigated the catalytic potential of observed divalent metal ions and water molecules bound to a 2 Å structure of the full-length hammerhead ribozyme by using X-ray crystallography in combination with molecular dynamics simulations. A single Mn2+ is observed to bind directly to the A9 phosphate in the active site, accompanying a hydrogen-bond network involving a well-ordered water molecule spanning N1 of G12 (the general base) and 2'-O of G8 (previously implicated in general acid catalysis) that we propose, based on molecular dynamics calculations, facilitates proton transfer in the cleavage reaction. Phosphate-bridging metal interactions and other mechanistic hypotheses are also tested with this approach. KW - nucleic_acids KW - solvation AU - Martick, Monika AU - Lee, Tai-Sung AU - York, Darrin AU - Scott, William PY - 2008/04/21/ UR - http://dx.doi.org/10.1016/j.chembiol.2008.03.010 ER -