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
Methionine-requiring protein 22
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
22247451
962
1004
22486802
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
(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.
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:

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