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

## TL;DR

The ribosome's peptidyl-transferase center uses an induced-fit mechanism to handle diverse amino acids efficiently.

## Contribution

The study connects the induced-fit mechanism in the ribosome to its ability to uniformly process various amino acids.

## Key findings

- Induced-fit eliminates unreactive rotamers in A-site aminoacyl esters.
- Induction constrains amino acids into a reactive conformation regardless of side-chain.
- The PTC's structure enables handling of both large and small substrates.

## Abstract

The catalytic site of most enzymes can essentially deal with 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 inducedfit 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.