EzCatDB: D00148

DB codeD00148
RLCP classification1.15.7910.1164
CATH domainDomain 13.30.540.10Catalytic domain
Domain 23.40.190.80Catalytic domain
E.C.3.1.3.7
CSA1qgx

CATH domainRelated DB codes (homologues)
3.30.540.10D00153,D00491,T00053
3.40.190.80D00153,D00491,T00053

Enzyme Name
Swiss-protKEGG

P32179
Protein name3''(2''),5''-bisphosphate nucleotidase (EC 3.1.3.7) (3''3'(2'),5'-bisphosphate nucleotidase
phosphoadenylate 3'-nucleotidase
3'-phosphoadenylylsulfate 3'-phosphatase
phosphoadenylate 3'-nucleotidase
3'(2'),5'-bisphosphonucleoside 3'(2')-phosphohydrolase
Synonyms2''),5-bisphosphonucleoside 3''(2'')-phosphohydrolase
DPNPase
Halotolerance protein HAL2

KEGG pathways
MAP codePathways
MAP00920Sulfur metabolism

Swiss-prot:Accession NumberP32179
Entry nameHAL2_YEAST
ActivityAdenosine 3'',5''-bisphosphate + H(2)O = adenosine 5''-phosphate + phosphate.
Subunit
Subcellular location
CofactorMagnesium.


CofactorsSubstratesProducts
KEGG-idC00305C00054C00001C00009C00020
CompoundMagnesiumAdenosine 3',5'-bisphosphateH2OOrthophosphateAdenosine 5'-phosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideH2Ophosphate group/phosphate ionamine group,nucleotide
1k9yA01Bound:3x_MGUnbound
Bound:PO4Unbound
1k9zA01Analogue:3x_ZNUnbound
UnboundUnbound
1ka0A01Analogue:_NAUnbound
UnboundUnbound
1ka1A01Analogue:_MG,_CAUnboundBound:HOH 11UnboundUnbound
1qgxA01Bound:2x_MGUnbound
Bound:PO4Unbound
1k9yA02UnboundUnbound
UnboundBound:AMP
1k9zA02UnboundUnbound
UnboundUnbound
1ka0A02UnboundUnbound
UnboundBound:AMP
1ka1A02UnboundBound:A3P
UnboundUnbound
1qgxA02UnboundUnbound
UnboundBound:AMP

Active-site residues
resource
Swiss-prot;P32179 & literature [4], [5]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysis
1k9yA01ASP 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
1k9zA01ASP 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
1ka0A01ASP 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
1ka1A01ASP 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
1qgxA01ASP 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
ReferencesSectionsNo. of steps in catalysis
[4]Fig.33, p.1092
[5]Fig.5, p.683

references
[1]
PubMed ID7493934
JournalJ Biol Chem
Year1995
Volume270
Pages29105-10
AuthorsPeng Z, Verma DP
TitleA 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.
[2]
PubMed ID7761465
JournalProc Natl Acad Sci U S A
Year1995
Volume92
Pages5149-53
AuthorsYork JD, Ponder JW, Majerus PW
TitleDefinition of a metal-dependent/Li(+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS AND AMP.
Medline ID20123982
PubMed ID10656801
JournalJ Mol Biol
Year2000
Volume295
Pages927-38
AuthorsAlbert A, Yenush L, Gil-Mascarell MR, Rodriguez PL, Patel S, Martinez-Ripoll M, Blundell TL, Serrano R
TitleX-ray structure of yeast Hal2p, a major target of lithium and sodium toxicity, and identification of framework interactions determining cation sensitivity.
Related PDB1qgx
Related Swiss-protP32179
[4]
CommentsX-ray Crystallography
PubMed ID12126627
JournalJ Mol Biol
Year2002
Volume320
Pages1087-94
AuthorsPatel S, Martinez-Ripoll M, Blundell TL, Albert A
TitleStructural enzymology of Li(+)-sensitive/Mg(2+)-dependent phosphatases.
Related PDB1k9y,1ka1
[5]
PubMed ID11812139
JournalJ Mol Biol
Year2002
Volume315
Pages677-85
AuthorsPatel S, Yenush L, Rodriguez PL, Serrano R, Blundell TL
TitleCrystal structure of an enzyme displaying both inositol-polyphosphate-1-phosphatase and 3'-phosphoadenosine-5'-phosphate phosphatase activities: a novel target of lithium therapy.

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.

createdupdated
2004-02-192009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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