Your browser doesn't support javascript.
loading
Structural basis for tRNA methylthiolation by the radical SAM enzyme MiaB.
Esakova, Olga A; Grove, Tyler L; Yennawar, Neela H; Arcinas, Arthur J; Wang, Bo; Krebs, Carsten; Almo, Steven C; Booker, Squire J.
Afiliación
  • Esakova OA; Department of Chemistry, The Pennsylvania State University, University Park, PA, USA. oae3@psu.edu.
  • Grove TL; Department of Biochemistry, Albert Einstein College of Medicine, New York, NY, USA. tylergrove223@gmail.com.
  • Yennawar NH; The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, USA.
  • Arcinas AJ; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.
  • Wang B; AGC Biologics, Seattle, WA, USA.
  • Krebs C; Department of Chemistry, The Pennsylvania State University, University Park, PA, USA.
  • Almo SC; Department of Chemistry, The Pennsylvania State University, University Park, PA, USA.
  • Booker SJ; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.
Nature ; 597(7877): 566-570, 2021 09.
Article en En | MEDLINE | ID: mdl-34526715
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 5'-deoxyadenosyl 5'-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 5'-deoxyadenosyl 5'-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.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Compuestos de Sulfhidrilo / Sulfurtransferasas / Bacteroides / ARN de Transferencia / Metiltransferasas Idioma: En Revista: Nature Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Compuestos de Sulfhidrilo / Sulfurtransferasas / Bacteroides / ARN de Transferencia / Metiltransferasas Idioma: En Revista: Nature Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido