Family

tRNA-2-methylthio-N(6)-dimethylallyladenosine synthase MiaB (IPR006463)

Short name: MiaB_methiolase

Family relationships

  • Methylthiotransferase (IPR005839)
    • tRNA-2-methylthio-N(6)-dimethylallyladenosine synthase MiaB (IPR006463)

Description

This entry represents the MiaB enzyme and homologues that are responsible for the modification of the isopentenylated adenine-37 base of most bacterial and eukaryotic tRNAs that read codons beginning with uracil (all except tRNA(I,V) Ser). Adenine-37 is next to the anticodon on the 3' side in these tRNA's, and lack of modification at this site leads to an increased spontaneous mutation frequency. Isopentenylated A-37 is modified by methylthiolation at position 2 leading to the formation of 2-methylthio-N6-(dimethylallyl)adenosine, either by MiaB alone or in concert with a separate methylase yet to be discovered [PMID: 10572129]. MiaB contains two 4Fe-4S clusters which are labile under oxidizing conditions [PMID: 11882645,[PMID: 17407324]. One cluster is coordinated with three cysteines and an exchangeable S-adenosyl-L-methionine, the other is thought to be the sulfur donor. The second cluster has a polysulfide group bound to it, which is methylated in the first reaction step. Concurrently, the SAM-[4Fe-4S] cluster forms the 5'-dAdo radical, which abstracts a hydrogen atom from the substrate, which is then methylthiolated by the methylated polysulfide group [PMID: 12766153,PMID: 15339930,PMID: 23991893]. Additionally, the sequence is homologous to the biotin synthetase, BioB, which utilises both an iron-sulfur cluster and S-adenosym methionine (SAM) to generate a radical which is responsible for initiating the insertion of sulfur into the substrate [PMID: 11313137]. It is reasonable to surmise that the methyl group of SAM becomes the methyl group of the product, but this has not been shown, and the possibility of a separate methylase exists. These enzymes contain a TRAM domain [PMID: 11313137] which is believed to be responsible for binding to tRNAs. The enzyme from Thermotoga maritima has been cloned, expressed, spectroscopically characterised and shown to complement the E. coli MiaB enzyme [PMID: 12766153].

GO terms

Biological Process

GO:0006400 tRNA modification

Molecular Function

GO:0051539 4 iron, 4 sulfur cluster binding
GO:0016740 transferase activity

Cellular Component

GO:0005737 cytoplasm

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
SFLD
HAMAP