Induced fit of the peptidyl-transferase center of the ribosome and conformational freedom of the esterified amino acids

RNA. 2017 Feb;23(2):229-239. doi: 10.1261/rna.057273.116. Epub 2016 Nov 22.

Abstract

The catalytic site of most enzymes can efficiently handle only one substrate. In contrast, the ribosome is capable of polymerizing at a similar rate at least 20 different kinds of amino acids from aminoacyl-tRNA carriers while using just one catalytic site, the peptidyl-transferase center (PTC). An induced-fit mechanism has been uncovered in the PTC, but a possible connection between this mechanism and the uniform handling of the substrates has not been investigated. We present an analysis of published ribosome structures supporting the hypothesis that the induced fit eliminates unreactive rotamers predominantly populated for some A-site aminoacyl esters before induction. We show that this hypothesis is fully consistent with the wealth of kinetic data obtained with these substrates. Our analysis reveals that induction constrains the amino acids into a reactive conformation in a side-chain independent manner. It allows us to highlight the rationale of the PTC structural organization, which confers to the ribosome the very unusual ability to handle large as well as small substrates.

Keywords: EF-P; aminoacyl-tRNA; induced fit; peptidyl-transferase center; ribosome.

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / metabolism*
  • Catalytic Domain
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Kinetics
  • Models, Molecular
  • Nucleic Acid Conformation
  • Peptidyl Transferases / chemistry
  • Peptidyl Transferases / genetics
  • Peptidyl Transferases / metabolism*
  • Protein Biosynthesis*
  • RNA, Transfer, Amino Acyl / chemistry
  • RNA, Transfer, Amino Acyl / metabolism*
  • Ribosomes / chemistry
  • Ribosomes / genetics
  • Ribosomes / metabolism*
  • Substrate Specificity
  • Thermodynamics

Substances

  • Amino Acids
  • RNA, Transfer, Amino Acyl
  • Peptidyl Transferases