{PDOC51604} {PS51675; SAM_MT_TRM10} {PS51623; SAM_MT_TRMH_1} {PS51624; SAM_MT_TRMH_2} {BEGIN} ************************************************************* * Class IV SAM-dependent methyltransferases family profiles * ************************************************************* Methyltransferases (EC 2.1.1.-) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as nitrogen, oxygen, sulfur or carbon leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids. Methyltransferases are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [1,2,3]. More than 230 different enzymatic reactions of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor [E1]. A review published in 2003 [2] divides all methyltransferases into 5 classes based on the structure of their catalytic domain (fold): - class I: Rossmann-like alpha/beta see - class II: TIM beta/alpha-barrel alpha/beta - class III: tetrapyrrole methylase alpha/beta - class IV: SPOUT alpha/beta - class V: SET domain all beta see A more recent paper [3] based on a study of the Saccharomyces cerevisiae methyltransferome argues for four more folds: - class VI: transmembrane all alpha see - class VII: DNA/RNA-binding 3-helical bundle all alpha - class VIII: SSo0622-like alpha+beta - class IX: thymidylate synthetase alpha+beta Up-to-date methyltransferases classified as Class IV (SPOUT) are homodimers and methylate only RNA. The common core of the SPOUT fold contains a five-stranded beta sheet, flanked by two layers of alpha helices. The core can be divided into two subdomains, both displaying an alpha/beta architecture: (1) the N-terminal strands exhibit a Rossmanoidal alpha/beta fold while (2) an important part of the C-terminal (~ 30 residues) is tucked back into the structure forming a conserved topological trefoil knot where SAM binding occurs. The active site, located at the interface of the two subunits, is formed by amino acids from both monomers [2,4]. The ribosomal RNA large subunit methyltransferase H (EC 2.1.1.77) from Staphylococcus aureus contains only the SPOUT fold core elements (see ) [4] but most Class IV methyltransferases such as the 23S rRNA (guanosine-2'-O-)-methyltransferase RlmB (EC 2.1.1.185) from Escherichia coli (see ) contain an extra alpha/beta module to the N-terminal subdomain [2,4]. Some enzymatic activities known to belong to the Class IV superfamily: - TRM10 methyltransferases: tRNA (guanine(9)-N(1))-methyltransferase (EC 2.1.1.221), tRNA (adenine(9)-N(1))-methyltransferase (EC 2.1.1.218) and RNA (guanine-9-)-methyltransferase domain-containing protein (EC 2.1.1.-). - TrmH methyltransferases: tRNA (guanosine(18)-2'-O)-methyltransferase (EC 2.1.1.34), 16S rRNA (guanine(527)-N(7))-methyltransferase (EC 2.1.1.170), 23S rRNA (guanine(2251)-2'-O)-methyltransferase (EC 2.1.1.185), tRNA (cytidine(32)/uridine(32)-2'-O)-methyltransferase (EC 2.1.1.200), tRNA (cytidine(34)-2'-O)-methyltransferase (EC 2.1.1.207) and other tRNA/rRNA methyltransferases. The profiles we developed to identify Class IV SAM-dependent methyltransferases families are directed against whole length proteins or domains. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: May 2013 / Profile replaced. [ 1] Kozbial P.Z., Mushegian A.R. "Natural history of S-adenosylmethionine-binding proteins." BMC Struct. Biol. 5:19-19(2005). PubMed=16225687; DOI=10.1186/1472-6807-5-19 [ 2] Schubert H.L., Blumenthal R.M., Cheng X. "Many paths to methyltransfer: a chronicle of convergence." Trends. Biochem. Sci. 28:329-335(2003). PubMed=12826405 [ 3] Wlodarski T., Kutner J., Towpik J., Knizewski L., Rychlewski L., Kudlicki A., Rowicka M., Dziembowski A., Ginalski K. "Comprehensive structural and substrate specificity classification of the Saccharomyces cerevisiae methyltransferome." PLoS One. 6:E23168-E23168(2011). PubMed=21858014; DOI=10.1371/journal.pone.0023168 [ 4] Tkaczuk K.L., Dunin-Horkawicz S., Purta E., Bujnicki J.M. "Structural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases." BMC Bioinformatics. 8:73-73(2007). PubMed=17338813; DOI=10.1186/1471-2105-8-73 [E1] https://enzyme.expasy.org/EC/2.1.1.- -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}