Structural basis for tRNA methylthiolation by the radical SAM enzyme MiaB

Olga A. Esakova (), Tyler L. Grove (), Neela H. Yennawar, Arthur J. Arcinas, Bo Wang, Carsten Krebs, Steven C. Almo and Squire J. Booker ()
Additional contact information
Olga A. Esakova: The Pennsylvania State University
Tyler L. Grove: Albert Einstein College of Medicine
Neela H. Yennawar: The Pennsylvania State University
Arthur J. Arcinas: The Pennsylvania State University
Bo Wang: The Pennsylvania State University
Carsten Krebs: The Pennsylvania State University
Steven C. Almo: Albert Einstein College of Medicine
Squire J. Booker: The Pennsylvania State University

Nature, 2021, vol. 597, issue 7877, 566-570

Abstract: Abstract Numerous post-transcriptional modifications of transfer RNAs have vital roles in translation. The 2-methylthio-N6-isopentenyladenosine (ms2i6A) modification occurs at position 37 (A37) in transfer RNAs that contain adenine in position 36 of the anticodon, and serves to promote efficient A:U codon–anticodon base-pairing and to prevent unintended base pairing by near cognates, thus enhancing translational fidelity1–4. The ms2i6A modification is installed onto isopentenyladenosine (i6A) by MiaB, a radical S-adenosylmethionine (SAM) methylthiotransferase. As a radical SAM protein, MiaB contains one [Fe4S4]RS cluster used in the reductive cleavage of SAM to form a 5ʹ-deoxyadenosyl 5ʹ-radical, which is responsible for removing the C2 hydrogen of the substrate5. MiaB also contains an auxiliary [Fe4S4]aux cluster, which has been implicated6–9 in sulfur transfer to C2 of i6A37. How this transfer takes place is largely unknown. Here we present several structures of MiaB from Bacteroides uniformis. These structures are consistent with a two-step mechanism, in which one molecule of SAM is first used to methylate a bridging µ-sulfido ion of the auxiliary cluster. In the second step, a second SAM molecule is cleaved to a 5ʹ-deoxyadenosyl 5ʹ-radical, which abstracts the C2 hydrogen of the substrate but only after C2 has undergone rehybridization from sp2 to sp3. This work advances our understanding of how enzymes functionalize inert C–H bonds with sulfur.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03904-6 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:597:y:2021:i:7877:d:10.1038_s41586-021-03904-6

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03904-6

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().