title: A proton wire to couple aminoacyl-tRNA accommodation and peptide-bond formation on the ribosome.
abstract: During peptide-bond formation on the ribosome, the α-amine of an aminoacyl-tRNA attacks the ester carbonyl carbon of a peptidyl-tRNA to yield a peptide lengthened by one amino acid. Although the ribosome's contribution to catalysis is predominantly entropic, the lack of high-resolution structural data for the complete active site in complex with full-length ligands has made it difficult to assess how the ribosome might influence the pathway of the reaction. Here, we present crystal structures of preattack and postcatalysis complexes of the Thermus thermophilus 70S ribosome at ~2.6-Å resolution. These structures reveal a network of hydrogen bonds along which proton transfer could take place to ensure the concerted, rate-limiting formation of a tetrahedral intermediate. We propose that, unlike earlier models, the ribosome and the A-site tRNA facilitate the deprotonation of the nucleophile through the activation of a water molecule.
authors.affiliation: 1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA.
authors.forename: Yury S
authors.initials: YS
authors.lastname: Polikanov
authors.affiliation: 1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA. [3] Department of Chemistry, Yale University, New Haven, Connecticut, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Steitz
authors.affiliation: 1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. [2].
authors.forename: C Axel
authors.initials: CA
authors.lastname: Innis
mesh_terms: D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011522:Protons; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*; D016963:Thermus thermophilus / Q000737:chemistry / Q000378:metabolism*; D014867:Water / Q000378:metabolism
chemical_list: D010455:Peptides; D011522:Protons; D012346:RNA, Transfer, Amino Acyl; D014867:Water