title: The mechanism of peptidyl transfer catalysis by the ribosome.
abstract: The ribosome catalyzes two fundamental biological reactions: peptidyl transfer, the formation of a peptide bond during protein synthesis, and peptidyl hydrolysis, the release of the complete protein from the peptidyl tRNA upon completion of translation. The ribosome is able to utilize and distinguish the two different nucleophiles for each reaction, the α-amine of the incoming aminoacyl tRNA versus the water molecule. The correct binding of substrates induces structural rearrangements of ribosomal active-site residues and the substrates themselves, resulting in an orientation suitable for catalysis. In addition, active-site residues appear to provide further assistance by ordering active-site water molecules and providing an electrostatic environment via a hydrogen network that stabilizes the reaction intermediates and possibly shuttles protons. Major questions remain concerning the timing, components, and mechanism of the proton transfer steps. This review summarizes the recent progress in structural, biochemical, and computational advances and presents the current mechanistic models for these two reactions.
authors.affiliation: Department of Biochemistry and Molecular Biology, Chicago, Illinois 60637, USA.
authors.forename: Edward Ki Yun
authors.initials: EK
authors.lastname: Leung
authors.forename: Nikolai
authors.initials: N
authors.lastname: Suslov
authors.forename: Nicole
authors.initials: N
authors.lastname: Tuttle
authors.forename: Raghuvir
authors.initials: R
authors.lastname: Sengupta
authors.forename: Joseph Anthony
authors.initials: JA
authors.lastname: Piccirilli
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008958:Models, Molecular; D015394:Molecular Structure; D014176:Protein Biosynthesis; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D012346:RNA, Transfer, Amino Acyl; C019037:tRNA, peptidyl-