DB code: S00637

CATH domain 3.40.50.150 : Rossmann fold Catalytic domain
E.C. 2.1.1.56
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.150 : Rossmann fold S00639 S00262 S00261 S00291 S00412 D00075 D00076 D00079 D00080 D00082 D00083 D00823

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q8SR66 mRNA cap guanine-N7 methyltransferase (EC 2.1.1.56) (mRNA
guanine-N(7)-)-methyltransferase
mRNA cap methyltransferase
NP_586153.1 (Protein)
NM_001041986.1 (DNA/RNA sequence)
PF03291 (Pox_MCEL)
[Graphical View]

KEGG enzyme name
mRNA (guanine-N7-)-methyltransferase
Messenger ribonucleate guanine 7-methyltransferase
Guanine-7-methyltransferase
Messenger RNA guanine 7-methyltransferase
S-Adenosyl-L-methionine:mRNA (guanine-7-N-)-methyltransferase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q8SR66 MCES_ENCCU S-adenosyl-L-methionine + G(5')pppR-RNA = S-adenosyl-L-homocysteine + m(7)G(5')pppR-RNA. Monomer. Nucleus (By similarity).

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00019 C02031 C00021 C02339
E.C.
Compound S-adenosyl-L-methionine G(5')pppR-RNA S-adenosyl-L-homocysteine m7G(5')pppR-RNA
Type amino acids,amine group,nucleoside,sulfonium ion amide group,amine group,nucleic acids,nucleotide amino acids,amine group,nucleoside,sulfide group nucleic acids,nucleotide
ChEBI 67040
 67040
 		16680
 57856
 16680
 57856
PubChem 34755
 34755
 		25246222
 439155
 25246222
 439155
1ri1A00 Unbound Analogue:GTG Bound:SAH Unbound
1ri2A00 Unbound Analogue:GTG Unbound Unbound
1ri3A00 Unbound Unbound Bound:SAH Unbound
1ri4A00 Bound:SAM Unbound Unbound Unbound
1ri5A00 Unbound Unbound Unbound Unbound
1z3cA00 Analogue:SA8 Unbound Unbound Unbound
2hv9A00 Analogue:SFG Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [6] & [8]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ri1A00 PHE 141;TYR 145
1ri2A00 PHE 141;TYR 145
1ri3A00 PHE 141;TYR 145
1ri4A00 PHE 141;TYR 145
1ri5A00 PHE 141;TYR 145
1z3cA00 PHE 141;TYR 145
2hv9A00 PHE 141;TYR 145

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
p85-87
[7]
p20410-20412
[8]
p35908

References
[1]
Resource
Comments
Medline ID
PubMed ID 8639642
Journal Biochemistry
Year 1996
Volume 35
Pages 6900-10
Authors Mao X, Shuman S
Title Vaccinia virus mRNA (guanine-7-)methyltransferase: mutational effects on cap methylation and AdoHcy-dependent photo-cross-linking of the cap to the methyl acceptor site.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10347220
Journal J Biol Chem
Year 1999
Volume 274
Pages 16553-62
Authors Saha N, Schwer B, Shuman S
Title Characterization of human, Schizosaccharomyces pombe, and Candida albicans mRNA cap methyltransferases and complete replacement of the yeast capping apparatus by mammalian enzymes.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 12859184
Journal Biochemistry
Year 2003
Volume 42
Pages 8394-402
Authors Takata Y, Huang Y, Komoto J, Yamada T, Konishi K, Ogawa H, Gomi T, Fujioka M, Takusagawa F
Title Catalytic mechanism of glycine N-methyltransferase.
Related PDB 1nbh 1nbi
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 12805428
Journal J Virol
Year 2003
Volume 77
Pages 7300-7
Authors Saha N, Shuman S, Schwer B
Title Yeast-based genetic system for functional analysis of poxvirus mRNA cap methyltransferase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 12826405
Journal Trends Biochem Sci
Year 2003
Volume 28
Pages 329-35
Authors Schubert HL, Blumenthal RM, Cheng X
Title Many paths to methyltransfer: a chronicle of convergence.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEXES WITH SUBSTRATES
Medline ID
PubMed ID 14731396
Journal Mol Cell
Year 2004
Volume 13
Pages 77-89
Authors Fabrega C, Hausmann S, Shen V, Shuman S, Lima CD
Title Structure and mechanism of mRNA cap (guanine-N7) methyltransferase.
Related PDB 1ri1 1ri2 1ri3 1ri4 1ri5
Related UniProtKB Q8SR66
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG
Medline ID
PubMed ID 15760890
Journal J Biol Chem
Year 2005
Volume 280
Pages 20404-12
Authors Hausmann S, Zheng S, Fabrega C, Schneller SW, Lima CD, Shuman S
Title Encephalitozoon cuniculi mRNA cap (guanine N-7) methyltransferase: methyl acceptor specificity, inhibition BY S-adenosylmethionine analogs, and structure-guided mutational analysis.
Related PDB 1z3c
Related UniProtKB Q8SR66
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG
Medline ID
PubMed ID 16971388
Journal J Biol Chem
Year 2006
Volume 281
Pages 35904-13
Authors Zheng S, Hausmann S, Liu Q, Ghosh A, Schwer B, Lima CD, Shuman S
Title Mutational analysis of Encephalitozoon cuniculi mRNA cap (guanine-N7) methyltransferase, structure of the enzyme bound to sinefungin, and evidence that cap methyltransferase is the target of sinefungin's antifungal activity.
Related PDB 2hv9
Related UniProtKB Q8SR66

Comments
This enzyme belongs to the class I methyltransferase family.
This enzyme is closely related to glycine N-methltransferase (EC 2.1.1.20; D00075 in EzCatDb).
According to the literature [6], [7] and [8], this enzyme facilitates methyl transfer from S-adenosyl-L-methionine (AdoMet) to the substrate guanine-N7 by coordinating the donor and acceptor in an environment that optimizes substrate proximity and orientation. Moreover, the shape of the guanine binding pocket is more important than particular base edge interactions. In this enzyme, the aliphatic carbon atoms of Phe141 and Tyr145 which engage in multiple van der Waals contacts with guanosine and AdoMet are more important in the in-lime mechanism of methyl transfer, rather than polar functional groups of active-site residues (see [6] and [8]).

Created Updated
2009-04-23 2011-12-20