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| Enzyme Name | | UniProtKB | KEGG |
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| P32179 |
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| Protein name | 3''(2''),5''-bisphosphate nucleotidase (EC 3.1.3.7) (3'' | 3'(2'),5'-bisphosphate nucleotidasephosphoadenylate 3'-nucleotidase3'-phosphoadenylylsulfate 3'-phosphatasephosphoadenylate 3'-nucleotidase3'(2'),5'-bisphosphonucleoside 3'(2')-phosphohydrolase |
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| Synonyms | 2''),5-bisphosphonucleoside 3''(2'')-phosphohydrolaseDPNPaseHalotolerance protein HAL2Methionine-requiring protein 22 |
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| RefSeq | NP_014577.1 (Protein)
NM_001183319.1 (DNA/RNA sequence)
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| Pfam | PF00459 (Inositol_P)
[Graphical view]
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| KEGG pathways | | MAP code | Pathways |
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| MAP00920 | Sulfur metabolism |
| UniProtKB:Accession Number | P32179 |
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| Entry name | HAL2_YEAST |
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| Activity | Adenosine 3'',5''-bisphosphate + H(2)O = adenosine 5''-phosphate + phosphate. |
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| Subunit |
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| Subcellular location |
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| Cofactor | Magnesium. |
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| References for Catalytic Mechanism | | References | Sections | No. of steps in catalysis |
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| [4] | Fig.33, p.1092 |
| | [5] | Fig.5, p.683 |
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| references | | [1] |
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| PubMed ID | 7493934 |
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| Journal | J Biol Chem |
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| Year | 1995 |
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| Volume | 270 |
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| Pages | 29105-10 |
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| Authors | Peng Z, Verma DP |
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| Title | A rice HAL2-like gene encodes a Ca(2+)-sensitive 3'(2'),5'-diphosphonucleoside 3'(2')-phosphohydrolase and complements yeast met22 and Escherichia coli cysQ mutations. |
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| [2] |
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| PubMed ID | 7761465 |
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| Journal | Proc Natl Acad Sci U S A |
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| Year | 1995 |
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| Volume | 92 |
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| Pages | 5149-53 |
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| Authors | York JD, Ponder JW, Majerus PW |
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| Title | Definition of a metal-dependent/Li(+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure. |
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| [3] |
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| Comments | X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS AND AMP. |
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| Medline ID | 20123982 |
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| PubMed ID | 10656801 |
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| Journal | J Mol Biol |
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| Year | 2000 |
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| Volume | 295 |
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| Pages | 927-38 |
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| Authors | Albert A, Yenush L, Gil-Mascarell MR, Rodriguez PL, Patel S, Martinez-Ripoll M, Blundell TL, Serrano R |
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| Title | X-ray structure of yeast Hal2p, a major target of lithium and sodium toxicity, and identification of framework interactions determining cation sensitivity. |
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| Related PDB | 1qgx |
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| Related UniProtKB | P32179 |
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| [4] |
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| Comments | X-ray Crystallography |
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| PubMed ID | 12126627 |
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| Journal | J Mol Biol |
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| Year | 2002 |
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| Volume | 320 |
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| Pages | 1087-94 |
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| Authors | Patel S, Martinez-Ripoll M, Blundell TL, Albert A |
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| Title | Structural enzymology of Li(+)-sensitive/Mg(2+)-dependent phosphatases. |
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| Related PDB | 1k9y,1ka1 |
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| [5] |
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| PubMed ID | 11812139 |
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| Journal | J Mol Biol |
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| Year | 2002 |
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| Volume | 315 |
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| Pages | 677-85 |
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| Authors | Patel S, Yenush L, Rodriguez PL, Serrano R, Blundell TL |
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| Title | Crystal structure of an enzyme displaying both inositol-polyphosphate-1-phosphatase and 3'-phosphoadenosine-5'-phosphate phosphatase activities: a novel target of lithium therapy. |
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| comments | This enzyme belongs to the inositol monophosphatase family. Although this enzyme binds only two magnesium ions according to Swissprot data, it might binds a third ion, if an excess of magnesium is available (see [4]).
According to the literature [4] & [5], the reaction proceeds by SN2-like mechanism as follows:
(1) Asp49 acts as the general base to activate a water through Thr147 (probably acting as a proton shuttle). In addition, Magnesium-1, which binds the water and 3'-phosphate of PAP substrate, also activates the water probably by lowering its pKa. (If the third magnesium ion is available, it may assists the role of the magnesium-1). Moreover, the mainchain amide groups of Gly146/Thr147 may assist the stabilization of the transition state.
(2) The activated water makes a nucleophilic attack on the phosphate group, leading to a trigonal bipyramidal transition state. This transition state is stabilized by Magnesium-1 and -2 ions.
(3) The target bond, phosphoester bond, is broken.
(4) Another water, which is bound to 2'-hydroxyl group of AMP product, seems to act as a acid to protonate the leaving 3'-oxygen, through 2'-hydroxyl group.
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| created | updated |
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| 2004-02-19 | 2009-02-26 |
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