DB code: S00412

RLCP classification 3.707.20000.110 : Transfer
CATH domain 3.40.50.150 : Rossmann fold Catalytic domain
E.C. 2.1.1.57
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.150 : Rossmann fold S00637 S00639 S00262 S00261 S00291 D00075 D00076 D00079 D00080 D00082 D00083 D00823

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P07617 Cap-specific mRNA (nucleoside-2''-O-)-methyltransferase
EC 2.1.1.57
Poly(A) polymerase regulatory subunit
Poly(A) polymerase small subunit
PAP-S
VP39
YP_232977.1 (Protein)
NC_006998.1 (DNA/RNA sequence)
PF01358 (PARP_regulatory)
[Graphical View]

KEGG enzyme name
mRNA (nucleoside-2'-O-)-methyltransferase
messenger ribonucleate nucleoside 2'-methyltransferase
messenger RNA (nucleoside-2'-)-methyltransferase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P07617 PAP2_VACCV S-adenosyl-L-methionine + m(7)G(5'')pppR-RNA = S-adenosyl-L-homocysteine + m(7)G(5'')pppRm-RNA. Methyltransferase activity: Monomer, poly(A) polymerase activity: Heterodimer of VP55 (catalytic) and VP39 (regulatory).

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00019 C02339 C00021 C04802
E.C.
Compound S-adenosyl-L-methionine m7G(5')pppR-RNA S-adenosyl-L-homocysteine m7G(5')pppRm-RNA (mRNA containing a 2'-O-methylpurine cap)
Type amino acids,amine group,nucleoside,sulfonium ion nucleic acids,nucleotide amino acids,amine group,nucleoside,sulfide group nucleic acids,nucleotide
ChEBI 67040
16680
57856
PubChem 34755
25246222
439155
1av6A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:MGT-__G-__A-__A-__A-__A-__A (chain B) Bound:SAH Unbound
1b42A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:SAH Unbound
1bkyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:SAH Unbound
1eamA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:SAH Unbound
1eqaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:MG7 Bound:SAH Unbound
1jszA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:SAH Unbound
1jteA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:SAH Unbound
1jtfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:M7G Bound:SAH Unbound
1p39A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:MGT Bound:SAH Unbound
1v39A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:M7G Bound:SAH Unbound
1vp3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:SAH Unbound
1vp9A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:SAH Unbound
1vptA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:SAM Unbound Unbound Unbound
2vp3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:M7G Bound:SAH Unbound
3magA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:SAH Unbound
3mctA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:SAH Unbound
4dcgA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:MG7 Bound:SAH Unbound

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

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1av6A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175
1b42A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175
1bkyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175
1eamA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175 mutant E233A
1eqaA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175 mutant E233Q
1jszA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175
1jteA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175 mutant F180W
1jtfA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175 mutant F180W
1p39A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175
1v39A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175
1vp3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175
1vp9A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175
1vptA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175 mutant R140A, K142A, R143A
2vp3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175
3magA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175
3mctA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175
4dcgA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 41;LYS 175 mutant D182A

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[8]
p.446

References
[1]
Resource
Comments
Medline ID
PubMed ID 1670500
Journal Cell
Year 1991
Volume 66
Pages 1269-78
Authors Gershon PD, Ahn BY, Garfield M, Moss B
Title Poly(A) polymerase and a dissociable polyadenylation stimulatory factor encoded by vaccinia virus.
Related PDB
Related UniProtKB P07617
[2]
Resource
Comments
Medline ID
PubMed ID 1313572
Journal Proc Natl Acad Sci U S A
Year 1992
Volume 89
Pages 2897-901
Authors Schnierle BS, Gershon PD, Moss B
Title Cap-specific mRNA (nucleoside-O2'-)-methyltransferase and poly(A) polymerase stimulatory activities of vaccinia virus are mediated by a single protein.
Related PDB
Related UniProtKB P07617
[3]
Resource
Comments
Medline ID
PubMed ID 8846300
Journal RNA
Year 1996
Volume 2
Pages 88-101
Authors Shi X, Yao P, Jose T, Gershon P
Title Methyltransferase-specific domains within VP-39, a bifunctional protein that participates in the modification of both mRNA ends.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8612277
Journal Cell
Year 1996
Volume 85
Pages 247-56
Authors Hodel AE, Gershon PD, Shi X, Quiocho FA
Title The 1.85 A structure of vaccinia protein VP39: a bifunctional enzyme that participates in the modification of both mRNA ends.
Related PDB 1vpt
Related UniProtKB P07617
[5]
Resource
Comments
Medline ID
PubMed ID 9118948
Journal EMBO J
Year 1997
Volume 16
Pages 1103-13
Authors Deng L, Gershon PD
Title Interplay of two uridylate-specific RNA binding sites in the translocation of poly(A) polymerase from vaccinia virus.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9145102
Journal Nat Struct Biol
Year 1997
Volume 4
Pages 350-4
Authors Hodel AE, Gershon PD, Shi X, Wang SM, Quiocho FA
Title Specific protein recognition of an mRNA cap through its alkylated base.
Related PDB 1p39 1v39 1vp3 1vp9 2vp3
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9287339
Journal J Biol Chem
Year 1997
Volume 272
Pages 23292-302
Authors Shi X, Bernhardt TG, Wang SM, Gershon PD
Title The surface region of the bifunctional vaccinia RNA modifying protein VP39 that interfaces with Poly(A) polymerase is remote from the RNA binding cleft used for its mRNA 5' cap methylation function.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 9660928
Journal Mol Cell
Year 1998
Volume 1
Pages 443-7
Authors Hodel AE, Gershon PD, Quiocho FA
Title Structural basis for sequence-nonspecific recognition of 5'-capped mRNA by a cap-modifying enzyme.
Related PDB 1av6
Related UniProtKB P07617
[9]
Resource
Comments
Medline ID
PubMed ID 9622508
Journal Biochemistry
Year 1998
Volume 37
Pages 8564-74
Authors Lockless SW, Cheng HT, Hodel AE, Quiocho FA, Gershon PD
Title Recognition of capped RNA substrates by VP39, the vaccinia virus-encoded mRNA cap-specific 2'-O-methyltransferase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 9657944
Journal Virology
Year 1998
Volume 246
Pages 253-65
Authors Gershon PD, Shi X, Hodel AE
Title Evidence that the RNA methylation and poly(A) polymerase stimulatory activities of vaccinia virus protein VP39 do not impinge upon one another.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 9917386
Journal J Mol Biol
Year 1999
Volume 285
Pages 1417-27
Authors Deng L, Johnson L, Neveu JM, Hardin S, Wang SM, Lane WS, Gershon PD
Title A polyadenylylation-specific RNA-contact site on the surface of the bifunctional vaccinia virus RNA modifying protein VP39 that is distinct from the mRNA 5' end-binding "cleft".
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 10377383
Journal Proc Natl Acad Sci U S A
Year 1999
Volume 96
Pages 7149-54
Authors Hu G, Gershon PD, Hodel AE, Quiocho FA
Title mRNA cap recognition: dominant role of enhanced stacking interactions between methylated bases and protein aromatic side chains.
Related PDB 1b42 1bky 1eam 1eqa 3mag 3mct 4dcg
Related UniProtKB
[13]
Resource
Comments Review
Medline ID
PubMed ID 10766517
Journal Curr Opin Struct Biol
Year 2000
Volume 10
Pages 75-7
Authors Rhodes D, Burley SK
Title Protein-nucleic acid interactions.
Related PDB
Related UniProtKB
[14]
Resource
Comments Review
Medline ID
PubMed ID 10679461
Journal Curr Opin Struct Biol
Year 2000
Volume 10
Pages 78-86
Authors Quiocho FA, Hu G, Gershon PD
Title Structural basis of mRNA cap recognition by proteins.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11076512
Journal Biochemistry
Year 2000
Volume 39
Pages 13730-6
Authors Hsu PC, Hodel MR, Thomas JW, Taylor LJ, Hagedorn CH, Hodel AE
Title Structural requirements for the specific recognition of an m7G mRNA cap.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 12056899
Journal Biochemistry
Year 2002
Volume 41
Pages 7677-87
Authors Hu G, Oguro A, Li C, Gershon PD, Quiocho FA
Title The "cap-binding slot" of an mRNA cap-binding protein: quantitative effects of aromatic side chain choice in the double-stacking sandwich with cap.
Related PDB 1jsz 1jte 1jtf
Related UniProtKB

Comments
This enzyme is a bifunctional protein, which methylates the ribose 2' OH group of the first transcribed nucleotide, and also act as a regulatory subunit of poly(A) polymerase, VP55, which creates the 3' poly(A) tail of mRNA's. This protein binds to poly(A), as a regulatory subunit.
According to the literature [8], the active site of this enzyme is similar to that of COMT (S00291 in EzCatDB), although it does not utilize a cofactor magnesium ion, unlike COMT. According to the literature [8], the reaction proceeds as follows:
(1) The positively charged sidechains of Lys41 and Lys175 act as modulator, which activate the acceptor, the oxygen atom of the 2' OH group, by lowering the pKa of the acceptor group, together with the positively charged sulfur atom of another substrate, SAM.
(2) The activated acceptor group makes a nucleophilic attack on the transferred group, the methyl group of SAM. (Probably, the reaction proceeds through an SN2-like mechanism, leading to the inversion of configuration of the methyl group, as in COMT.)

Created Updated
2002-08-30 2009-02-26