Methylthiotransferase, N-terminal (IPR013848)

Short name: Methylthiotransferase_N

Overlapping homologous superfamilies

Domain relationships



The methylthiotransferase (MTTase) or miaB-like family is named after the (dimethylallyl)adenosine tRNA MTTase miaB protein, which catalyses a C-H to C-S bond conversion in the methylthiolation of tRNA. A related bacterial enzyme rimO performs a similar methylthiolation, but on a protein substrate. RimO acts on the ribosomal protein S12 and forms a separate MTTase subfamily. The miaB-subfamily includes mammalian CDK5 regulatory subunit-associated proteins and similar proteins in other eukaryotes. Two other subfamilies, yqeV and CDKAL1, are named after a Bacillus subtilis and a human protein, respectively. While yqeV-like proteins are found in bacteria, CDKAL1 subfamily members occur in eukaryotes and in archaebacteria. The likely MTTases from these 4 subfamilies contain an N-terminal MTTase domain, a central radical generating fold and a C-terminal TRAM domain (see PDOC50926). The core forms a radical SAM fold (or AdoMet radical), containing a cysteine motif CxxxCxxC that binds a [4Fe-4S] cluster [PMID: 11882645, PMID: 18252828, PMID: 11222759]. A reducing equivalent from the [4Fe-4S]+ cluster is used to cleave S-adenosylmethionine (SAM) to generate methionine and a 5'-deoxyadenosyl radical. The latter is thought to produce a reactive substrate radical that is amenable to sulphur insertion [PMID: 18252828, PMID: 11222759]. The N-terminal MTTase domain contains 3 cysteines that bind a second [4Fe-4S] cluster, in addition to the radical-generating [4Fe-4S] cluster, which could be involved in the thiolation reaction. The C-terminal TRAM domain is not shared with other radical SAM proteins outside the MTTase family. The TRAM domain can bind to RNA substrate and seems to be important for substrate recognition. The tertiary structure of the central radical SAM fold has six beta/alpha motifs resembling a three-quarter TIM barrel core (see PDOC00155) [PMID: 15289575]. The N-terminal MTTase domain might form an additional [beta/alpha]2 TIM barrel unit [PMID: 18252828].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0051539 4 iron, 4 sulfur cluster binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles