DB code: D00148

RLCP classification 1.15.7910.1164 : Hydrolysis
CATH domain 3.30.540.10 : Fructose-1,6-Bisphosphatase; Chain A, domain 1 Catalytic domain
3.40.190.80 : D-Maltodextrin-Binding Protein; domain 2 Catalytic domain
E.C. 3.1.3.7
CSA 1qgx
M-CSA 1qgx
MACiE

CATH domain Related DB codes (homologues)
3.40.190.80 : D-Maltodextrin-Binding Protein; domain 2 D00153 D00491 T00053
3.30.540.10 : Fructose-1,6-Bisphosphatase; Chain A, domain 1 D00153 D00491 T00053

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P32179 3''(2''),5''-bisphosphate nucleotidase (EC 3.1.3.7) (3''
2''),5-bisphosphonucleoside 3''(2'')-phosphohydrolase
DPNPase
Halotolerance protein HAL2
NP_014577.1 (Protein)
NM_001183319.1 (DNA/RNA sequence)
PF00459 (Inositol_P)
[Graphical View]

KEGG enzyme name
3'(2'),5'-bisphosphate nucleotidase
phosphoadenylate 3'-nucleotidase
3'-phosphoadenylylsulfate 3'-phosphatase
phosphoadenylate 3'-nucleotidase
3'(2'),5'-bisphosphonucleoside 3'(2')-phosphohydrolase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P32179 HAL2_YEAST Adenosine 3'',5''-bisphosphate + H(2)O = adenosine 5''-phosphate + phosphate. Magnesium.

KEGG Pathways
Map code Pathways E.C.
MAP00920 Sulfur metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00054 C00001 C00009 C00020
E.C.
Compound Magnesium Adenosine 3',5'-bisphosphate H2O Orthophosphate Adenosine 5'-phosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide H2O phosphate group/phosphate ion amine group,nucleotide
ChEBI 18420
17985
15377
26078
16027
PubChem 888
159296
962
22247451
22486802
1004
6083
1k9yA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:3x_MG Unbound Bound:PO4 Unbound
1k9zA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:3x_ZN Unbound Unbound Unbound
1ka0A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_NA Unbound Unbound Unbound
1ka1A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_MG,_CA Unbound Bound:HOH_11 Unbound Unbound
1qgxA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_MG Unbound Bound:PO4 Unbound
1k9yA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:AMP
1k9zA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1ka0A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:AMP
1ka1A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:A3P Unbound Unbound
1qgxA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:AMP

Reference for Active-site residues
resource references E.C.
Swiss-prot;P32179 & literature [4], [5]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1k9yA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 49;THR 147 GLU 72(Magnesium-1 & -3);ASP 142(Magnesium-1 & -2);ASP 145(Magnesium-2);ILE 144(Magnesium-1) GLY 146;THR 147
1k9zA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 49;THR 147 GLU 72(Magnesium-1 & -3);ASP 142(Magnesium-1 & -2);ASP 145(Magnesium-2);ILE 144(Magnesium-1) GLY 146;THR 147
1ka0A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 49;THR 147 GLU 72(Magnesium-1 & -3);ASP 142(Magnesium-1 & -2);ASP 145(Magnesium-2);ILE 144(Magnesium-1) GLY 146;THR 147
1ka1A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 49;THR 147 GLU 72(Magnesium-1 & -3);ASP 142(Magnesium-1 & -2);ASP 145(Magnesium-2);ILE 144(Magnesium-1) GLY 146;THR 147
1qgxA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 49;THR 147 GLU 72(Magnesium-1 & -3);ASP 142(Magnesium-1 & -2);ASP 145(Magnesium-2);ILE 144(Magnesium-1) GLY 146;THR 147
1k9yA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 294(Magnesium-2)
1k9zA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 294(Magnesium-2)
1ka0A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 294(Magnesium-2)
1ka1A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 294(Magnesium-2)
1qgxA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 294(Magnesium-2)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
Fig.33, p.1092
[5]
Fig.5, p.683

References
[1]
Resource
Comments
Medline ID
PubMed ID 7493934
Journal J Biol Chem
Year 1995
Volume 270
Pages 29105-10
Authors Peng Z, Verma DP
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.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7761465
Journal Proc Natl Acad Sci U S A
Year 1995
Volume 92
Pages 5149-53
Authors York JD, Ponder JW, Majerus PW
Title Definition of a metal-dependent/Li(+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS AND AMP.
Medline ID 20123982
PubMed ID 10656801
Journal J Mol Biol
Year 2000
Volume 295
Pages 927-38
Authors Albert A, Yenush L, Gil-Mascarell MR, Rodriguez PL, Patel S, Martinez-Ripoll M, Blundell TL, Serrano R
Title X-ray structure of yeast Hal2p, a major target of lithium and sodium toxicity, and identification of framework interactions determining cation sensitivity.
Related PDB 1qgx
Related UniProtKB P32179
[4]
Resource
Comments X-ray Crystallography
Medline ID
PubMed ID 12126627
Journal J Mol Biol
Year 2002
Volume 320
Pages 1087-94
Authors Patel S, Martinez-Ripoll M, Blundell TL, Albert A
Title Structural enzymology of Li(+)-sensitive/Mg(2+)-dependent phosphatases.
Related PDB 1k9y 1ka1
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 11812139
Journal J Mol Biol
Year 2002
Volume 315
Pages 677-85
Authors Patel S, Yenush L, Rodriguez PL, Serrano R, Blundell TL
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.
Related PDB
Related UniProtKB

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.

Created Updated
2004-02-19 2009-02-26