7MJY

MiaB in the complex with s-adenosyl-L-homocysteine and RNA

Summary for 7MJY

• Entry DOI: 10.2210/pdb7mjy/pdb
• Descriptor: tRNA-2-methylthio-N(6)-dimethylallyladenosine synthase, RNA (5'-R(P*UP*AP*UP*UP*C)-3'), TRIETHYLENE GLYCOL, ... (9 entities in total)
• Functional Keywords: trna-2-methylthio-n(6)-dimethylallyladenosine synthase, transferase, transferase-rna complex, transferase/rna
• Biological source: Bacteroides uniformis; More
• Total number of polymer chains: 2
• Total formula weight: 57677.49

Authors

Esakova, O.A.,Grove, T.L.,Yennawar, N.H.,Arcinas, A.J.,Wang, B.,Krebs, C.,Almo, S.C.,Booker, S.J. (deposition date: 2021-04-20, release date: 2021-09-15, Last modification date: 2023-10-18)

Primary citation

Esakova, O.A.,Grove, T.L.,Yennawar, N.H.,Arcinas, A.J.,Wang, B.,Krebs, C.,Almo, S.C.,Booker, S.J.
Structural basis for tRNA methylthiolation by the radical SAM enzyme MiaB.
Nature, 597:566-570, 2021

PubMed Abstract: Numerous post-transcriptional modifications of transfer RNAs have vital roles in translation. The 2-methylthio-N-isopentenyladenosine (msiA) 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 fidelity. The msiA modification is installed onto isopentenyladenosine (iA) by MiaB, a radical S-adenosylmethionine (SAM) methylthiotransferase. As a radical SAM protein, MiaB contains one [FeS] cluster used in the reductive cleavage of SAM to form a 5'-deoxyadenosyl 5'-radical, which is responsible for removing the C hydrogen of the substrate. MiaB also contains an auxiliary [FeS] cluster, which has been implicated in sulfur transfer to C of iA37. 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 C hydrogen of the substrate but only after C has undergone rehybridization from sp to sp. This work advances our understanding of how enzymes functionalize inert C-H bonds with sulfur.

PubMed: 34526715
DOI: 10.1038/s41586-021-03904-6

Experimental method

X-RAY DIFFRACTION (1.86 Å)