EzCatDB: M00218
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DB codeM00218
RLCP classification3.103.70200.1160 : Transfer
CATH domainDomain 13.30.70.590 : Alpha-Beta Plaits
Domain 23.30.460.10 : Beta Polymerase; domain 2Catalytic domain
Domain 31.10.1410.10 : Poly(a)-polymerase, middle domain
Domain 4-.-.-.-
E.C.2.7.7.19

CATH domainRelated DB codes (homologues)
1.10.1410.10 : Poly(a)-polymerase, middle domainT00202
3.30.460.10 : Beta Polymerase; domain 2T00202
3.30.70.590 : Alpha-Beta PlaitsT00202

Enzyme Name
UniProtKBKEGG

P25500
Protein namePoly(A) polymerase alphapolynucleotide adenylyltransferase
NTP polymerase
RNA adenylating enzyme
AMP polynucleotidylexotransferase
ATP-polynucleotide adenylyltransferase
ATP:polynucleotidylexotransferase
poly(A) polymerase
poly(A) synthetase
polyadenylate nucleotidyltransferase
polyadenylate polymerase
polyadenylate synthetase
polyadenylic acid polymerase
polyadenylic polymerase
terminal riboadenylate transferase
poly(A) hydrolase
RNA formation factors, PF1
adenosine triphosphate:ribonucleic acid adenylyltransferase
SynonymsPAP-alpha
EC 2.7.7.19
Polynucleotide adenylyltransferase alpha
RefSeqNP_788820.1 (Protein)
NM_176647.2 (DNA/RNA sequence)
PfamPF01909 (NTP_transf_2)
PF04928 (PAP_central)
PF04926 (PAP_RNA-bind)
[Graphical view]


UniProtKB:Accession NumberP25500
Entry namePAPOA_BOVIN
ActivityATP + RNA(n) = diphosphate + RNA(n+1).
SubunitMonomer. Found in a complex with CPSF1, FIP1L1 and PAPOLA. Interacts with NUDT21/CPSF5 and FIP1L1 (By similarity).
Subcellular locationNucleus.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00046C00013C00046
CompoundMagnesiumATPRNA(n)PyrophosphateRNA(n+1)
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidenucleic acidsphosphate group/phosphate ionnucleic acids
ChEBI18420
15422

29888

PubChem888
5957

21961011
1023

             
1f5aA01UnboundUnboundUnboundUnboundUnbound
1f5aA02Analogue:3x_MNBound:3ATUnboundAnalogue:3POUnbound
1f5aA03UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot: P25500 & P29468
pdbCatalytic residuesCofactor-binding residues
          
1f5aA01 
 
1f5aA02ASP 115
ASP 113;ASP 115;ASP 167(Mg binding)
1f5aA03 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.2600
[4]p.4199

references
[1]
PubMed ID8665867
JournalEMBO J
Year1996
Volume15
Pages2593-603
AuthorsMartin G, Keller W
TitleMutational analysis of mammalian poly(A) polymerase identifies a region for primer binding and catalytic domain, homologous to the family X polymerases, and to other nucleotidyltransferases.
Related UniProtKBP25500
[2]
PubMed ID9061026
JournalBiochim Biophys Acta
Year1997
Volume1350
Pages293-305
AuthorsWittmann T, Wahle E
TitlePurification and characterization of full-length mammalian poly(A) polymerase.
[3]
PubMed ID10595540
JournalProtein Sci
Year1999
Volume8
Pages2380-91
AuthorsMartin G, Jeno P, Keller W
TitleMapping of ATP binding regions in poly(A) polymerases by photoaffinity labeling and by mutational analysis identifies a domain conserved in many nucleotidyltransferases.
[4]
PubMed ID10944102
JournalEMBO J
Year2000
Volume19
Pages4193-203
AuthorsMartin G, Keller W, Doublie S
TitleCrystal structure of mammalian poly(A) polymerase in complex with an analog of ATP.
Related PDB1f5a
Related UniProtKBP25500
[5]
PubMed ID10958780
JournalScience
Year2000
Volume289
Pages1346-9
AuthorsBard J, Zhelkovsky AM, Helmling S, Earnest TN, Moore CL, Bohm A
TitleStructure of yeast poly(A) polymerase alone and in complex with 3'-dATP.
Related PDB1fa0

comments
This enzyme is homologous to the counterpart enzyme from yeast (T00202 in EzCatDB), showing the same reaction mechanism as that of the counterpart.
According to the literature [1], three acidic residues chelate two Mg2+ ions, which in turn coordinate the alpha-phosphorus of the incoming nucleotide and the 3'-hydroxyl group of the primer. The proton of the attacking hydroxyl group can be abstracted by the nearby acidic residue in the catalytic site. The activated hydroxyl acts as the nucleophile in the subsequent phosphoester bond formation. The reaction results in the inversion of the stereochemistry at the alpha-phosphorus of the now covalently linked nucleoside and ends with the release of Mg2+-pyrophosphate.
The paper [4] also suggests that the catalytic reaction involves an in-line attack of the 3'-hydroxyl group of the primer on the incoming ATP, without a covalent intermediate.
Considering the structure, Asp102 (PDB;1fa0 in T00202) acts as a general base, which activate the 3'-hydroxyl group.

createdupdated
2002-08-292009-03-09


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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
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