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PROSITE documentation PDOC51604

Class IV SAM-dependent methyltransferases family profiles





Description

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 α/β see <PDOC51555>
  • class II: TIM β/α-barrel α/β
  • class III: tetrapyrrole methylase α/β
  • class IV: SPOUT α/β
  • class V: SET domain all β see <PDOC51565>

A more recent paper [3] based on a study of the Saccharomyces cerevisiae methyltransferome argues for four more folds:

  • class VI: transmembrane all α see <PDOC51598>
  • class VII: DNA/RNA-binding 3-helical bundle all α
  • class VIII: SSo0622-like α+β
  • class IX: thymidylate synthetase α+β

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 β sheet, flanked by two layers of α helices. The core can be divided into two subdomains, both displaying an α/β architecture: (1) the N-terminal strands exhibit a Rossmanoidal α/β 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 <PDB:1VH0>) [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 <PDB:1GZ0>) contain an extra α/β 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.

Last update:

May 2013 / Profile replaced.

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Technical section

PROSITE methods (with tools and information) covered by this documentation:

SAM_MT_TRM10, PS51675; SAM-dependent methyltransferase TRM10-type domain profile  (MATRIX)

SAM_MT_TRMH_1, PS51623; tRNA guanosine-2'-O-methyltransferase (EC 2.1.1.34) family profile  (MATRIX)

SAM_MT_TRMH_2, PS51624; RNA methyltransferase TRMH family profile  (MATRIX)


References

1AuthorsKozbial P.Z. Mushegian A.R.
TitleNatural history of S-adenosylmethionine-binding proteins.
SourceBMC Struct. Biol. 5:19-19(2005).
PubMed ID16225687
DOI10.1186/1472-6807-5-19

2AuthorsSchubert H.L. Blumenthal R.M. Cheng X.
TitleMany paths to methyltransfer: a chronicle of convergence.
SourceTrends. Biochem. Sci. 28:329-335(2003).
PubMed ID12826405

3AuthorsWlodarski T. Kutner J. Towpik J. Knizewski L. Rychlewski L. Kudlicki A. Rowicka M. Dziembowski A. Ginalski K.
TitleComprehensive structural and substrate specificity classification of the Saccharomyces cerevisiae methyltransferome.
SourcePLoS One. 6:E23168-E23168(2011).
PubMed ID21858014
DOI10.1371/journal.pone.0023168

4AuthorsTkaczuk K.L. Dunin-Horkawicz S. Purta E. Bujnicki J.M.
TitleStructural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases.
SourceBMC Bioinformatics. 8:73-73(2007).
PubMed ID17338813
DOI10.1186/1471-2105-8-73

E1Titlehttps://enzyme.expasy.org/EC/2.1.1.-



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