Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Principles of tRNA(Ala) Selection by Alanyl-tRNA Synthetase Based on the Critical G3.U70 Base Pair
Indian Inst Technol Guwahati, Dept Biosci & Bioengn, Gauhati 781039, Assam, India.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.ORCID iD: 0000-0003-2091-0610
Indian Inst Technol Guwahati, Dept Biosci & Bioengn, Gauhati 781039, Assam, India.
2019 (English)In: ACS OMEGA, ISSN 2470-1343, Vol. 4, no 13, p. 15539-15548Article in journal (Refereed) Published
Abstract [en]

Throughout evolution, the presence of a single G3.U70 mismatch in the acceptor stem of tRNA(Ala) is the major determinant for aminoacylation with alanine by alanyl-tRNA synthetase (AlaRS). Recently reported crystal structures of the complexes AlaRS-tRNA(Ala)/G3.U70 and AlaRS-tRNA tRNA(Ala)/A3.U70 suggest two very different conformations, representing a reactive and a nonreactive state, respectively. On the basis of these structures, it has been proposed that the G3.U70 base pair guides the-CCA end of the tRNA acceptor stem into the active site of AIaRS, thereby enabling aminoacylation. The crystal structures open up the possibility of directly computing the energetics of tRNA specificity by AIaRS. We have carried out molecular dynamics free-energy simulations to quantitatively estimate tRNA discrimination by AlaRS, focusing on the mutations of the single critical base pair G3.U70 to uncover the energetics underlying the accuracy of tRNA selection. The calculations show that the reactive complex is highly selective in favor of the cognate tRNA(Ala)/G3.U70 over its noncognate analogues (A3.U70/G3.C70/A3.C70). In contrast, the nonreactive complex is predicted to be unselective between tRNA(Ala)G3.U70 and tRNA(Ala)/A3.U70. Utilizing our calculated relative binding free energies, we show how a simple three-step kinetic scheme for aminoacylation, involving both an initial nonspecific binding step and a subsequent transition to a selective reactive complex, accounts for the observed kinetics of the process.

Place, publisher, year, edition, pages
2019. Vol. 4, no 13, p. 15539-15548
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-396664DOI: 10.1021/acsomega.9b01827ISI: 000488852700025PubMedID: 31572855OAI: oai:DiVA.org:uu-396664DiVA, id: diva2:1369546
Funder
Knut and Alice Wallenberg FoundationSwedish Research CouncilAvailable from: 2019-11-12 Created: 2019-11-12 Last updated: 2019-11-12Bibliographically approved

Open Access in DiVA

fulltext(4352 kB)7 downloads
File information
File name FULLTEXT01.pdfFile size 4352 kBChecksum SHA-512
8efe4e911abeadb93fb76dec56b76d08c6c1ab058e3a8d1e903029b7333680be5a07ace3d8234d79fab8cf1e20ca665a1c7729dc3e8861b6250a226615d9f9dc
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Åqvist, Johan
By organisation
Computational Biology and Bioinformatics
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 7 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 14 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf