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| Enzyme Name | | Swiss-prot | KEGG |
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| P25500 |
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| Protein name | Poly(A) polymerase alpha | polynucleotide adenylyltransferaseNTP polymeraseRNA adenylating enzymeAMP polynucleotidylexotransferaseATP-polynucleotide adenylyltransferaseATP:polynucleotidylexotransferasepoly(A) polymerasepoly(A) synthetasepolyadenylate nucleotidyltransferasepolyadenylate polymerasepolyadenylate synthetasepolyadenylic acid polymerasepolyadenylic polymeraseterminal riboadenylate transferasepoly(A) hydrolaseRNA formation factors, PF1adenosine triphosphate:ribonucleic acid adenylyltransferase |
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| Synonyms | PAP-alphaEC 2.7.7.19Polynucleotide adenylyltransferase alpha |
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| Swiss-prot:Accession Number | P25500 |
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| Entry name | PAPOA_BOVIN |
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| Activity | ATP + RNA(n) = diphosphate + RNA(n+1). |
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| Subunit | Monomer. Found in a complex with CPSF1, FIP1L1 and PAPOLA. Interacts with NUDT21/CPSF5 and FIP1L1 (By similarity). |
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| Subcellular location | Nucleus. |
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| Cofactor |
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| Cofactors | Substrates | Products |
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| KEGG-id | C00305 | C00002 | C00046 | C00013 | C00046 |
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| Compound | Magnesium | ATP | RNA(n) | Pyrophosphate | RNA(n+1) |
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| Type | divalent metal (Ca2+, Mg2+) | amine group,nucleotide | nucleic acids | phosphate group/phosphate ion | nucleic acids |
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| 1f5aA1 |  | Unbound | Unbound | Unbound | Unbound | Unbound |
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| 1f5aA2 | | Analogue:3x_MN | Bound:3AT | Unbound | Analogue:3PO | Unbound |
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| 1f5aA3 | | Unbound | Unbound | Unbound | Unbound | Unbound |
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| Active-site residues | | resource |
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| Swiss-prot: P25500 & P29468 | | pdb | Catalytic residues | Cofactor-binding residues |
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| 1f5aA1 | |
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| 1f5aA2 | | ASP 115
| ASP 113;ASP 115;ASP 167(Mg binding)
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| 1f5aA3 | |
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| References for Catalytic Mechanism | | References | Sections | No. of steps in catalysis |
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| [1] | p.2600 |
| | [4] | p.4199 |
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| references | | [1] |
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| PubMed ID | 8665867 |
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| Journal | EMBO J |
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| Year | 1996 |
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| Volume | 15 |
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| Pages | 2593-603 |
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| Authors | Martin G, Keller W |
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| Title | Mutational 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. |
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| Related Swiss-prot | P25500 |
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| [2] |
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| PubMed ID | 9061026 |
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| Journal | Biochim Biophys Acta |
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| Year | 1997 |
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| Volume | 1350 |
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| Pages | 293-305 |
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| Authors | Wittmann T, Wahle E |
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| Title | Purification and characterization of full-length mammalian poly(A) polymerase. |
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| [3] |
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| PubMed ID | 10595540 |
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| Journal | Protein Sci |
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| Year | 1999 |
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| Volume | 8 |
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| Pages | 2380-91 |
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| Authors | Martin G, Jeno P, Keller W |
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| Title | Mapping of ATP binding regions in poly(A) polymerases by photoaffinity labeling and by mutational analysis identifies a domain conserved in many nucleotidyltransferases. |
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| [4] |
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| PubMed ID | 10944102 |
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| Journal | EMBO J |
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| Year | 2000 |
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| Volume | 19 |
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| Pages | 4193-203 |
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| Authors | Martin G, Keller W, Doublie S |
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| Title | Crystal structure of mammalian poly(A) polymerase in complex with an analog of ATP. |
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| Related PDB | 1f5a |
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| Related Swiss-prot | P25500 |
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| [5] |
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| PubMed ID | 10958780 |
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| Journal | Science |
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| Year | 2000 |
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| Volume | 289 |
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| Pages | 1346-9 |
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| Authors | Bard J, Zhelkovsky AM, Helmling S, Earnest TN, Moore CL, Bohm A |
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| Title | Structure of yeast poly(A) polymerase alone and in complex with 3'-dATP. |
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| Related PDB | 1fa0 |
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| 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.
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| created | updated |
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| 2002-08-29 | 2009-03-09 |
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