EzCatDB: S00412
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DB codeS00412
RLCP classification3.707.20000.110 : Transfer
CATH domainDomain 13.40.50.150 : Rossmann foldCatalytic domain
E.C.2.1.1.57

CATH domainRelated DB codes (homologues)
3.40.50.150 : Rossmann foldS00637,S00639,S00262,S00261,S00291,D00075,D00076,D00079,D00080,D00082,D00083,D00823

Enzyme Name
UniProtKBKEGG

P07617
Protein nameCap-specific mRNA (nucleoside-2''-O-)-methyltransferasemRNA (nucleoside-2'-O-)-methyltransferase
messenger ribonucleate nucleoside 2'-methyltransferase
messenger RNA (nucleoside-2'-)-methyltransferase
SynonymsEC 2.1.1.57
Poly(A) polymerase regulatory subunit
Poly(A) polymerase small subunit
PAP-S
VP39
RefSeqYP_232977.1 (Protein)
NC_006998.1 (DNA/RNA sequence)
PfamPF01358 (PARP_regulatory)
[Graphical view]


UniProtKB:Accession NumberP07617
Entry namePAP2_VACCV
ActivityS-adenosyl-L-methionine + m(7)G(5'')pppR-RNA = S-adenosyl-L-homocysteine + m(7)G(5'')pppRm-RNA.
SubunitMethyltransferase activity: Monomer, poly(A) polymerase activity: Heterodimer of VP55 (catalytic) and VP39 (regulatory).
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00019C02339C00021C04802
CompoundS-adenosyl-L-methioninem7G(5')pppR-RNAS-adenosyl-L-homocysteinem7G(5')pppRm-RNA (mRNA containing a 2'-O-methylpurine cap)
Typeamino acids,amine group,nucleoside,sulfonium ionnucleic acids,nucleotideamino acids,amine group,nucleoside,sulfide groupnucleic acids,nucleotide
ChEBI67040

16680
57856

PubChem34755

439155
25246222

            
1av6AUnboundAnalogue:MGT-__G-__A-__A-__A-__A-__A(chain B)Bound:SAHUnbound
1b42AUnboundUnboundBound:SAHUnbound
1bkyAUnboundUnboundBound:SAHUnbound
1eamAUnboundUnboundBound:SAHUnbound
1eqaAUnboundAnalogue:MG7Bound:SAHUnbound
1jszAUnboundUnboundBound:SAHUnbound
1jteAUnboundUnboundBound:SAHUnbound
1jtfAUnboundAnalogue:M7GBound:SAHUnbound
1p39AUnboundAnalogue:MGTBound:SAHUnbound
1v39AUnboundAnalogue:M7GBound:SAHUnbound
1vp3AUnboundUnboundBound:SAHUnbound
1vp9AUnboundUnboundBound:SAHUnbound
1vptABound:SAMUnboundUnboundUnbound
2vp3AUnboundAnalogue:M7GBound:SAHUnbound
3magAUnboundUnboundBound:SAHUnbound
3mctAUnboundUnboundBound:SAHUnbound
4dcgAUnboundAnalogue:MG7Bound:SAHUnbound

Active-site residues
resource
literature [8]
pdbCatalytic residuescomment
          
1av6ALYS 41;LYS 175
 
1b42ALYS 41;LYS 175
 
1bkyALYS 41;LYS 175
 
1eamALYS 41;LYS 175
mutant E233A
1eqaALYS 41;LYS 175
mutant E233Q
1jszALYS 41;LYS 175
 
1jteALYS 41;LYS 175
mutant F180W
1jtfALYS 41;LYS 175
mutant F180W
1p39ALYS 41;LYS 175
 
1v39ALYS 41;LYS 175
 
1vp3ALYS 41;LYS 175
 
1vp9ALYS 41;LYS 175
 
1vptALYS 41;LYS 175
mutant R140A, K142A, R143A
2vp3ALYS 41;LYS 175
 
3magALYS 41;LYS 175
 
3mctALYS 41;LYS 175
 
4dcgALYS 41;LYS 175
mutant D182A

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[8]p.446

references
[1]
PubMed ID1670500
JournalCell
Year1991
Volume66
Pages1269-78
AuthorsGershon PD, Ahn BY, Garfield M, Moss B
TitlePoly(A) polymerase and a dissociable polyadenylation stimulatory factor encoded by vaccinia virus.
Related UniProtKBP07617
[2]
PubMed ID1313572
JournalProc Natl Acad Sci U S A
Year1992
Volume89
Pages2897-901
AuthorsSchnierle BS, Gershon PD, Moss B
TitleCap-specific mRNA (nucleoside-O2'-)-methyltransferase and poly(A) polymerase stimulatory activities of vaccinia virus are mediated by a single protein.
Related UniProtKBP07617
[3]
PubMed ID8846300
JournalRNA
Year1996
Volume2
Pages88-101
AuthorsShi X, Yao P, Jose T, Gershon P
TitleMethyltransferase-specific domains within VP-39, a bifunctional protein that participates in the modification of both mRNA ends.
[4]
PubMed ID8612277
JournalCell
Year1996
Volume85
Pages247-56
AuthorsHodel AE, Gershon PD, Shi X, Quiocho FA
TitleThe 1.85 A structure of vaccinia protein VP39: a bifunctional enzyme that participates in the modification of both mRNA ends.
Related PDB1vpt
Related UniProtKBP07617
[5]
PubMed ID9118948
JournalEMBO J
Year1997
Volume16
Pages1103-13
AuthorsDeng L, Gershon PD
TitleInterplay of two uridylate-specific RNA binding sites in the translocation of poly(A) polymerase from vaccinia virus.
[6]
PubMed ID9145102
JournalNat Struct Biol
Year1997
Volume4
Pages350-4
AuthorsHodel AE, Gershon PD, Shi X, Wang SM, Quiocho FA
TitleSpecific protein recognition of an mRNA cap through its alkylated base.
Related PDB1p39,1v39,1vp3,1vp9,2vp3
[7]
PubMed ID9287339
JournalJ Biol Chem
Year1997
Volume272
Pages23292-302
AuthorsShi X, Bernhardt TG, Wang SM, Gershon PD
TitleThe 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.
[8]
PubMed ID9660928
JournalMol Cell
Year1998
Volume1
Pages443-7
AuthorsHodel AE, Gershon PD, Quiocho FA
TitleStructural basis for sequence-nonspecific recognition of 5'-capped mRNA by a cap-modifying enzyme.
Related PDB1av6
Related UniProtKBP07617
[9]
PubMed ID9622508
JournalBiochemistry
Year1998
Volume37
Pages8564-74
AuthorsLockless SW, Cheng HT, Hodel AE, Quiocho FA, Gershon PD
TitleRecognition of capped RNA substrates by VP39, the vaccinia virus-encoded mRNA cap-specific 2'-O-methyltransferase.
[10]
PubMed ID9657944
JournalVirology
Year1998
Volume246
Pages253-65
AuthorsGershon PD, Shi X, Hodel AE
TitleEvidence that the RNA methylation and poly(A) polymerase stimulatory activities of vaccinia virus protein VP39 do not impinge upon one another.
[11]
PubMed ID9917386
JournalJ Mol Biol
Year1999
Volume285
Pages1417-27
AuthorsDeng L, Johnson L, Neveu JM, Hardin S, Wang SM, Lane WS, Gershon PD
TitleA 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".
[12]
PubMed ID10377383
JournalProc Natl Acad Sci U S A
Year1999
Volume96
Pages7149-54
AuthorsHu G, Gershon PD, Hodel AE, Quiocho FA
TitlemRNA cap recognition: dominant role of enhanced stacking interactions between methylated bases and protein aromatic side chains.
Related PDB1b42,1bky,1eam,1eqa,3mag,3mct,4dcg
[13]
CommentsReview
PubMed ID10766517
JournalCurr Opin Struct Biol
Year2000
Volume10
Pages75-7
AuthorsRhodes D, Burley SK
TitleProtein-nucleic acid interactions.
[14]
CommentsReview
PubMed ID10679461
JournalCurr Opin Struct Biol
Year2000
Volume10
Pages78-86
AuthorsQuiocho FA, Hu G, Gershon PD
TitleStructural basis of mRNA cap recognition by proteins.
[15]
PubMed ID11076512
JournalBiochemistry
Year2000
Volume39
Pages13730-6
AuthorsHsu PC, Hodel MR, Thomas JW, Taylor LJ, Hagedorn CH, Hodel AE
TitleStructural requirements for the specific recognition of an m7G mRNA cap.
[16]
PubMed ID12056899
JournalBiochemistry
Year2002
Volume41
Pages7677-87
AuthorsHu G, Oguro A, Li C, Gershon PD, Quiocho FA
TitleThe "cap-binding slot" of an mRNA cap-binding protein: quantitative effects of aromatic side chain choice in the double-stacking sandwich with cap.
Related PDB1jsz,1jte,1jtf

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.)

createdupdated
2002-08-302009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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