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
CATH 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)
3.30.540.10 : Fructose-1,6-Bisphosphatase; Chain A, domain 1	D00153 D00491 T00053
3.40.190.80 : D-Maltodextrin-Binding Protein; domain 2	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 18420	17985 17985	15377 15377	26078 26078	16027 16027
PubChem	888 888	159296 159296	22247451 962 22247451 962	1004 22486802 1004 22486802	6083 6083

1k9yA01	Bound:3x_MG	Unbound		Bound:PO4	Unbound
1k9zA01	Analogue:3x_ZN	Unbound		Unbound	Unbound
1ka0A01	Analogue:_NA	Unbound		Unbound	Unbound
1ka1A01	Analogue:_MG,_CA	Unbound	Bound:HOH_11	Unbound	Unbound
1qgxA01	Bound:2x_MG	Unbound		Bound:PO4	Unbound
1k9yA02	Unbound	Unbound		Unbound	Bound:AMP
1k9zA02	Unbound	Unbound		Unbound	Unbound
1ka0A02	Unbound	Unbound		Unbound	Bound:AMP
1ka1A02	Unbound	Bound:A3P		Unbound	Unbound
1qgxA02	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	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	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	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	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	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		ASP 294(Magnesium-2)
1k9zA02		ASP 294(Magnesium-2)
1ka0A02		ASP 294(Magnesium-2)
1ka1A02		ASP 294(Magnesium-2)
1qgxA02		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.

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