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Title | Atomistic simulations of the Escherichia coli ribosome provide selection criteria for translationally active substrates. |
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Journal, issue, pages | Nat Chem, Vol. 15, Issue 7, Page 913-921, Year 2023 |
Publish date | Jun 12, 2023 |
Authors | Zoe L Watson / Isaac J Knudson / Fred R Ward / Scott J Miller / Jamie H D Cate / Alanna Schepartz / Ara M Abramyan / |
PubMed Abstract | As genetic code expansion advances beyond L-α-amino acids to backbone modifications and new polymerization chemistries, delineating what substrates the ribosome can accommodate remains a challenge. ...As genetic code expansion advances beyond L-α-amino acids to backbone modifications and new polymerization chemistries, delineating what substrates the ribosome can accommodate remains a challenge. The Escherichia coli ribosome tolerates non-L-α-amino acids in vitro, but few structural insights that explain how are available, and the boundary conditions for efficient bond formation are so far unknown. Here we determine a high-resolution cryogenic electron microscopy structure of the E. coli ribosome containing α-amino acid monomers and use metadynamics simulations to define energy surface minima and understand incorporation efficiencies. Reactive monomers across diverse structural classes favour a conformational space where the aminoacyl-tRNA nucleophile is <4 Å from the peptidyl-tRNA carbonyl with a Bürgi-Dunitz angle of 76-115°. Monomers with free energy minima that fall outside this conformational space do not react efficiently. This insight should accelerate the in vivo and in vitro ribosomal synthesis of sequence-defined, non-peptide heterooligomers. |
External links | Nat Chem / PubMed:37308707 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.1 - 2.3 Å |
Structure data | EMDB-28254, PDB-8emm: EMDB-28255: 70S map for: "Atomistic simulations of the E. coli ribosome provide selection criteria for translationally active substrates" EMDB-28256: 30S-focused map for: "Atomistic simulations of the E. coli ribosome provide selection criteria for translationally active substrates" EMDB-28257: 50S-focused map for: "Atomistic simulations of the E. coli ribosome provide selection criteria for translationally active substrates" |
Chemicals | ChemComp-MG: ChemComp-SPD: ChemComp-SPM: ChemComp-K: ChemComp-ZN: ChemComp-MET: ChemComp-PAR: ChemComp-HOH: |
Source |
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Keywords | RIBOSOME / tRNA / e. coli |