Peptide bond formation on the ribosome: structure and mechanism.
The peptidyl transferase reaction on the ribosome is catalyzed by RNA. Pre-steady-state kinetic studies using Escherichia coli ribosomes suggest that catalysis (>10(5)-fold overall acceleration) is, to a large part, a result of substrate positioning, in agreement with crystal structures of large ribosomal subunits with bound substrate or product analogs. The rate of peptide bond formation is inhibited approximately 100-fold by protonation of a single ribosomal group with a pK(a) of 7.5, indicating general acid-base catalysis and/or a pH-dependent conformational change within the active site. According to the kinetics of mutant ribosomes, these effects may be attributed to a candidate catalytic base (A2451) suggested by the crystal structure.
Rodnina
Marina V
MV
Institutes of Physical Biochemistry and Molecular Biology, University of Witten/Herdecke, Stockumer Strasse 10, 58448, Witten, Germany. rodnina@uni-wh.de
Wintermeyer
Wolfgang
W
D020029:Base Pairing; D001665:Binding Sites; D002384:Catalysis; D004926:Escherichia coli / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010458:Peptidyl Transferases / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism*
D010455:Peptides; D012313:RNA; D010458:Peptidyl Transferases