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Model for the Functional Active State of the TS Ribozyme from Molecular Simulation
Author(s) -
Gaines Colin S.,
York Darrin M.
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201705608
Subject(s) - ribozyme , active site , residue (chemistry) , molecule , chemistry , computational biology , structural genomics , rna , functional genomics , computer science , protein structure , catalysis , genomics , biology , biochemistry , genome , gene , organic chemistry
Recently, a crystal structure has been reported of a new catalytic RNA, the TS ribozyme, that has been identified through comparative genomics and is believed to be a metalloribozyme having novel mechanistic features. Although this data provides invaluable structural information, analysis suggests a conformational change is required to arrive at a catalytically relevant state. We report results of molecular simulations that predict a spontaneous local rearrangement of the active site, leading to solution structures consistent with available functional data and providing competing mechanistic hypotheses that can be experimentally tested. The two competing hypotheses differ in the proposed identity of the catalytic general acid: either a water molecule coordinating a Mg 2+ ion bound at the Watson–Crick edge of residue C7, or the N3 position of residue C7 itself.