EzCatDB: S00435
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DB codeS00435
RLCP classification1.15.9500.540 : Hydrolysis
CATH domainDomain 13.60.21.10 : Purple Acid Phosphatase; chain A, domain 2Catalytic domain
E.C.3.1.3.2

CATH domainRelated DB codes (homologues)
3.60.21.10 : Purple Acid Phosphatase; chain A, domain 2D00146,D00147,D00151

Enzyme Name
UniProtKBKEGG

P29288P09889
Protein nameTartrate-resistant acid phosphatase type 5Tartrate-resistant acid phosphatase type 5acid phosphatase
acid phosphomonoesterase
phosphomonoesterase
glycerophosphatase
acid monophosphatase
acid phosphohydrolase
acid phosphomonoester hydrolase
uteroferrin
acid nucleoside diphosphate phosphatase
orthophosphoric-monoester phosphohydrolase (acid optimum)
SynonymsTR-AP
EC 3.1.3.2
Tartrate-resistant acid ATPase
TrATPase
Acid phosphatase 5, tartrate resistant
TR-AP
EC 3.1.3.2
Tartrate-resistant acid ATPase
TrATPase
Acid phosphatase 5, tartrate resistant
Uteroferrin
UF
RefSeqNP_001257818.1 (Protein)
NM_001270889.1 (DNA/RNA sequence)
NP_062017.2 (Protein)
NM_019144.2 (DNA/RNA sequence)
NP_999374.1 (Protein)
NM_214209.1 (DNA/RNA sequence)
PfamPF00149 (Metallophos)
[Graphical view]
PF00149 (Metallophos)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00361gamma-Hexachlorocyclohexane degradation
MAP00740Riboflavin metabolism

UniProtKB:Accession NumberP29288P09889
Entry namePPA5_RATPPA5_PIG
ActivityA phosphate monoester + H(2)O = an alcohol + phosphate.A phosphate monoester + H(2)O = an alcohol + phosphate.
SubunitExists either as monomer or, after proteolytic processing, as a dimer of two chains linked by disulfide bond(s).
Subcellular locationLysosome.Secreted.
CofactorBinds 2 iron ions per subunit.Binds 2 iron ions per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00023C01153C00001C00069C00009
CompoundIronOrthophosphoric monoesterH2OAlcoholOrthophosphate
Typeheavy metalcarbohydrate,phosphate group/phosphate ionH2Ocarbohydratephosphate group/phosphate ion
ChEBI18248
82664

15377

26078
PubChem23925

962
22247451

22486802
1004
             
1qfcABound:2x_FEUnbound UnboundBound:PO4
1qhwAAnalogue:_FE,_ZNUnbound UnboundAnalogue:SO4
1uteABound:FEOUnbound Bound:IPABound:PO4

Active-site residues
resource
Swiss-prot & literature
pdbCatalytic residuesCofactor-binding residues
          
1qfcAHIS  92;HIS 195;ASP 246
ASP  14;ASP  52;TYR  55;HIS 223(Fe3+ binding);ASP  52;ASN  91;HIS 186;HIS 221(Fe2+ binding)
1qhwAHIS 113;HIS 216;ASP 267
ASP  35;ASP  73;TYR  76;HIS 244(Fe3+ binding);ASP  73;ASN 112;HIS 207;HIS 242(Fe2+ binding)
1uteAHIS  92;HIS 195;ASP 246
ASP  14;ASP  52;TYR  55;HIS 223(Fe3+ binding);ASP  52;ASN  91;HIS 186;HIS 221(Fe2+ binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[5]p.1490-1491
[6]Fig.6, p.740-7443
[11]p.203-208
[13]p.9923-9924, Scheme 3
[15]Fig.8, p.143-1442
[20]p.5643

references
[1]
PubMed ID1648483
JournalEur J Biochem
Year1991
Volume199
Pages105-13
AuthorsDietrich M, Munstermann D, Suerbaum H, Witzel H
TitlePurple acid phosphatase from bovine spleen. Interactions at the active site in relation to the reaction mechanism.
[2]
PubMed ID1332769
JournalBiochemistry
Year1992
Volume31
Pages11731-9
AuthorsCrans DC, Simone CM, Holz RC, Que L Jr
TitleInteraction of porcine uterine fluid purple acid phosphatase with vanadate and vanadyl cation.
[3]
PubMed ID7821667
JournalBiochem Soc Trans
Year1994
Volume22
Pages700-4
AuthorsWilkins PC, Dalton H
TitleVariations on a theme of Fe-O-Fe proteins.
[4]
PubMed ID7771777
JournalArch Biochem Biophys
Year1995
Volume319
Pages133-41
AuthorsWynne CJ, Hamilton SE, Dionysius DA, Beck JL, de Jersey J
TitleStudies on the catalytic mechanism of pig purple acid phosphatase.
[5]
PubMed ID7770774
JournalScience
Year1995
Volume268
Pages1489-92
AuthorsStrater N, Klabunde T, Tucker P, Witzel H, Krebs B
TitleCrystal structure of a purple acid phosphatase containing a dinuclear Fe(III)-Zn(II) active site.
[6]
CommentsX-ray crystallography
Medline ID96275658
PubMed ID8683579
JournalJ Mol Biol
Year1996
Volume259
Pages737-48
AuthorsKlabunde T, Strater N, Frohlich R, Witzel H, Krebs B
TitleMechanism of Fe(III)-Zn(II) purple acid phosphatase based on crystal structures.
Related PDB1kbp,3kbp,4kbp
Related UniProtKBP80366
[7]
PubMed ID9020859
JournalBiochem J
Year1997
Volume321
Pages305-11
AuthorsEk-Rylander B, Barkhem T, Ljusberg J, Ohman L, Andersson KK, Andersson G
TitleComparative studies of rat recombinant purple acid phosphatase and bone tartrate-resistant acid phosphatase.
[8]
PubMed ID9169589
JournalBiochem J
Year1997
Volume323
Pages593-6
AuthorsBattistuzzi G, Dietrich M, Locke R, Witzel H
TitleEvidence for a conserved binding motif of the dinuclear metal site in mammalian and plant purple acid phosphatases: 1H NMR studies of the di-iron derivative of the Fe(III)Zn(II) enzyme from kidney bean.
[9]
PubMed ID9698368
JournalBiochemistry
Year1998
Volume37
Pages11223-31
AuthorsMerkx M, Averill BA
TitleThe activity of oxidized bovine spleen purple acid phosphatase is due to an Fe(III)Zn(II) 'impurity'.
[10]
PubMed ID10376348
JournalJ Inorg Biochem
Year1999
Volume73
Pages245-52
AuthorsBeck JL, Durack MC, Hamilton SE, de Jersey J
TitleIrreversible inactivation of purple acid phosphatase by hydrogen peroxide and ascorbate.
[11]
CommentsX-ray crystallography (2.7 Angstroms)
PubMed ID10388567
JournalJ Mol Biol
Year1999
Volume290
Pages201-11
AuthorsUppenberg J, Lindqvist F, Svensson C, Ek-Rylander B, Andersson G
TitleCrystal structure of a mammalian purple acid phosphatase.
Related PDB1qfc
[12]
CommentsX-ray crystallography (1.55 Angstroms)
PubMed ID10425678
JournalStructure Fold Des
Year1999
Volume7
Pages757-67
AuthorsGuddat LW, McAlpine AS, Hume D, Hamilton S, de Jersey J, Martin JL
TitleCrystal structure of mammalian purple acid phosphatase.
Related PDB1ute
[13]
PubMed ID10433698
JournalBiochemistry
Year1999
Volume38
Pages9914-25
AuthorsMerkx M, Pinkse MW, Averill BA
TitleEvidence for nonbridged coordination of p-nitrophenyl phosphate to the dinuclear Fe(III)-M(II) center in bovine spleen purple acid phosphatase during enzymatic turnover.
[14]
PubMed ID10433699
JournalBiochemistry
Year1999
Volume38
Pages9926-36
AuthorsPinkse MW, Merkx M, Averill BA
TitleFluoride inhibition of bovine spleen purple acid phosphatase: characterization of a ternary enzyme-phosphate-fluoride complex as a model for the active enzyme-substrate-hydroxide complex.
[15]
CommentsX-ray crystallography (2.2 Angstroms)
PubMed ID10438611
JournalJ Mol Biol
Year1999
Volume291
Pages135-47
AuthorsLindqvist Y, Johansson E, Kaija H, Vihko P, Schneider G
TitleThree-dimensional structure of a mammalian purple acid phosphatase at 2.2 A resolution with a mu-(hydr)oxo bridged di-iron center.
Related PDB1qhw
[16]
PubMed ID11278566
JournalJ Biol Chem
Year2001
Volume276
Pages19084-8
AuthorsSchenk G, Boutchard CL, Carrington LE, Noble CJ, Moubaraki B, Murray KS, de Jersey J, Hanson GR, Hamilton S
TitleA purple acid phosphatase from sweet potato contains an antiferromagnetically coupled binuclear Fe-Mn center.
[17]
PubMed ID11491293
JournalJ Mol Biol
Year2001
Volume309
Pages239-54
AuthorsKnofel T, Strater N
TitleMechanism of hydrolysis of phosphate esters by the dimetal center of 5'-nucleotidase based on crystal structures.
[18]
PubMed ID11560512
JournalBiochemistry
Year2001
Volume40
Pages11614-22
AuthorsFunhoff EG, Ljusberg J, Wang Y, Andersson G, Averill BA
TitleMutational analysis of the interaction between active site residues and the loop region in mammalian purple acid phosphatases.
[19]
PubMed ID11828464
JournalChembiochem
Year2001
Volume2
Pages355-63
AuthorsFunhoff EG, Klaassen CH, Samyn B, Van Beeumen J, Averill BA
TitleThe highly exposed loop region in mammalian purple acid phosphatase controls the catalytic activity.
[20]
PubMed ID12401063
JournalInorg Chem
Year2002
Volume41
Pages5641-3
AuthorsLanznaster M, Neves A, Bortoluzzi AJ, Szpoganicz B, Schwingel E
TitleNew Fe(III)Zn(II) complex containing a single terminal Fe-O(phenolate) bond as a structural and functional model for the active site of red kidney bean purple acid phosphatase.
[21]
PubMed ID12440878
JournalJ Am Chem Soc
Year2002
Volume124
Pages13974-5
AuthorsDikiy A, Funhoff EG, Averill BA, Ciurli S
TitleNew insights into the mechanism of purple acid phosphatase through (1)H NMR spectroscopy of the recombinant human enzyme.
[22]
PubMed ID12484780
JournalBiochemistry
Year2002
Volume41
Pages15404-9
AuthorsReiter TA, Reiter NJ, Rusnak F
TitleMn2+ is a native metal ion activator for bacteriophage lambda protein phosphatase.
[23]
PubMed ID12693232
JournalInorg Chem
Year2003
Volume42
Pages499-507
AuthorsVerge F, Lebrun C, Fontecave M, Menage S
TitleHydrolysis of phosphodiesters by diiron complexes: design of nonequivalent iron sites in purple acid phosphatase models.

comments
Although the purple acid phosphatases from plant (D00146) and from mammal (S00435) are homologous to each other, they adopt slightly different catalytic mechanisms. The plant enzyme uses Fe(III) and zinc ions as cofactors, whilst the mammalian enzyme uses Fe(III) and Fe(II).
According to the literature [5], [6] & [15], the catalysis proceeds through SN2-like reaction, resulting in the inversion of configuration at the phosphorous atom. This is against the covalent phosphorylated intermediate formation.
In the initial stage, the phoshate group of the substrate will bind to the divalent metal (M(II)), whilst the nucleophilic hydroxyl ion is bound to the ferric ion (Fe(III)) (see [6] & [15]). This hydroxide is in a position suitable for in-line attack on the phosphorous atom. In the first step, the hydroxyl group makes a nucleophilic attack on the phosphorous atom, forming a pentacovalent transition state, which is stablized by histidine residues, His202, His295 and His296 (plant purple acid phosphatase;PDB 1kbp), His113 and His216 (mammalian purple acid phosphatase;PDB 1qhw).
In the next step, a catalytic acid will protonate to the leaving group of the product. His296 acts as the catalytic acid in the plant enzyme (PDB 1kbp), whilst Asp267 plays the catalytic role in the mammalian enzyme (PDB 1qhw).
In the final step, the phosphate group, bound in a bidentate binding mode to the two metal ions, will be displaced from the Fe(III) ion by a coming water molecule (see [6] & [15]).

createdupdated
2002-07-092009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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