7mjz | pdb_00007mjz
The structure of MiaB with pentasulfide bridge
Structural highlights
Function[A0A174GYG1_BACUN] Catalyzes the methylthiolation of N6-(dimethylallyl)adenosine (i(6)A), leading to the formation of 2-methylthio-N6-(dimethylallyl)adenosine (ms(2)i(6)A) at position 37 in tRNAs that read codons beginning with uridine.[ARBA:ARBA00003234][HAMAP-Rule:MF_01864] Publication Abstract from PubMedNumerous post-transcriptional modifications of transfer RNAs have vital roles in translation. The 2-methylthio-N(6)-isopentenyladenosine (ms(2)i(6)A) 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(1-4). The ms(2)i(6)A modification is installed onto isopentenyladenosine (i(6)A) 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 C(2) hydrogen of the substrate(5). MiaB also contains an auxiliary [Fe4S4]aux cluster, which has been implicated(6-9) in sulfur transfer to C(2) of i(6)A37. 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 micro-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(2) hydrogen of the substrate but only after C(2) has undergone rehybridization from sp(2) to sp(3). This work advances our understanding of how enzymes functionalize inert C-H bonds with sulfur. Structural basis for tRNA methylthiolation by the radical SAM enzyme MiaB.,Esakova OA, Grove TL, Yennawar NH, Arcinas AJ, Wang B, Krebs C, Almo SC, Booker SJ Nature. 2021 Sep;597(7877):566-570. doi: 10.1038/s41586-021-03904-6. Epub 2021, Sep 15. PMID:34526715[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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