Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Mechanistic alternatives for peptide bond formation on the ribosome
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi. Uppsala University, Sweden.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
Antal upphovsmän: 42018 (Engelska)Ingår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 46, nr 11, s. 5345-5354Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The peptidyl transfer reaction on the large ribosomal subunit depends on the protonation state of the amine nucleophile and exhibits a large kinetic solvent isotope effect (KSIE similar to 8). In contrast, the related peptidyl-tRNA hydrolysis reaction involved in termination shows a KSIE of similar to 4 and a pH-rate profile indicative of base catalysis. It is, however, unclear why these reactions should proceed with different mechanisms, as the experimental data suggests. One explanation is that two competing mechanisms may be operational in the peptidyl transferase center (PTC). Herein, we explored this possibility by re-examining the previously proposed proton shuttle mechanism and testing the feasibility of general base catalysis also for peptide bond formation. We employed a large cluster model of the active site and different reaction mechanisms were evaluated by density functional theory calculations. In these calculations, the proton shuttle and general base mechanisms both yield activation energies comparable to the experimental values. However, only the proton shuttle mechanism is found to be consistent with the experimentally observed pH-rate profile and the KSIE. This suggests that the PTC promotes the proton shuttle mechanism for peptide bond formation, while prohibiting general base catalysis, although the detailed mechanism by which general base catalysis is excluded remains unclear.

Ort, förlag, år, upplaga, sidor
2018. Vol. 46, nr 11, s. 5345-5354
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
URN: urn:nbn:se:su:diva-159150DOI: 10.1093/nar/gky367ISI: 000438362400007PubMedID: 29746669OAI: oai:DiVA.org:su-159150DiVA, id: diva2:1242521
Tillgänglig från: 2018-08-28 Skapad: 2018-08-28 Senast uppdaterad: 2018-08-28Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltextPubMed

Sök vidare i DiVA

Av författaren/redaktören
Kazemi, MasoudHimo, Fahmi
Av organisationen
Institutionen för organisk kemi
I samma tidskrift
Nucleic Acids Research
Biologiska vetenskaper

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 6 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf