DB code: S00363

RLCP classification 1.15.30200.84 : Hydrolysis
CATH domain 3.40.50.1240 : Rossmann fold Catalytic domain
E.C. 3.1.3.2
CSA 1rpt
M-CSA 1rpt
MACiE

CATH domain Related DB codes (homologues)
3.40.50.1240 : Rossmann fold S00365 S00366 D00460 D00514

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P20646 Prostatic acid phosphatase
EC 3.1.3.2
NP_001128373.1 (Protein)
NM_001134901.1 (DNA/RNA sequence)
NP_064457.1 (Protein)
NM_020072.1 (DNA/RNA sequence)
PF00328 (His_Phos_2)
[Graphical View]
P15309 Prostatic acid phosphatase
EC 3.1.3.2
NP_001090.2 (Protein)
NM_001099.4 (DNA/RNA sequence)
NP_001127666.1 (Protein)
NM_001134194.1 (DNA/RNA sequence)
PF00328 (His_Phos_2)
[Graphical View]

KEGG enzyme name
acid phosphatase
acid phosphomonoesterase
phosphomonoesterase
glycerophosphatase
acid monophosphatase
acid phosphohydrolase
acid phosphomonoester hydrolase
uteroferrin
acid nucleoside diphosphate phosphatase
orthophosphoric-monoester phosphohydrolase (acid optimum)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P20646 PPAP_RAT A phosphate monoester + H(2)O = an alcohol + phosphate. Homodimer.
P15309 PPAP_HUMAN A phosphate monoester + H(2)O = an alcohol + phosphate. Homodimer.

KEGG Pathways
Map code Pathways E.C.
MAP00361 gamma-Hexachlorocyclohexane degradation
MAP00740 Riboflavin metabolism

Compound table
Substrates Products Intermediates
KEGG-id C01153 C00001 C00069 C00009
E.C.
Compound Orthophosphoric monoester H2O Alcohol Orthophosphate
Type carbohydrate,phosphate group/phosphate ion H2O carbohydrate phosphate group/phosphate ion
ChEBI 15377
 15377
 		26078
 26078
PubChem 22247451
 962
 22247451
 962
 		1004
 22486802
 1004
 22486802
1rpaA Unbound Unbound Unbound
1rptA Unbound Unbound Analogue:VO4
1nd5A Analogue:2BF Unbound Unbound
1nd5B Analogue:2BF Unbound Unbound
1nd5C Analogue:2BF Unbound Unbound
1nd5D Analogue:2BF Unbound Unbound
2hpaA Unbound Unbound Unbound
2hpaB Unbound Unbound Unbound
2hpaC Unbound Unbound Unbound
2hpaD Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [2],[3]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1rpaA ARG 11;ARG 15;ARG 79;HIS 257(Stabilizers);HIS 12;ASP 258
1rptA ARG 11;ARG 15;ARG 79;HIS 257(Stabilizers);HIS 12;ASP 258
1nd5A ARG 11;ARG 15;ARG 79;HIS 257(Stabilizers);HIS 12;ASP 258
1nd5B ARG 1010;ARG 1014;ARG 1078;HIS 1255(Stabilizers);HIS 1011;ASP 1256
1nd5C ARG 2010;ARG 2014;ARG 2078;HIS 2256(Stabilizers);HIS 2011;ASP 2257
1nd5D ARG 3010;ARG 3014;ARG 3078;HIS 3256(Stabilizers);HIS 3011;ASP 3257
2hpaA ARG 1011;ARG 1015;ARG 1079;HIS 1257(Stabilizers);HIS 1012;ASP 1258
2hpaB ARG 2011;ARG 2015;ARG 2079;HIS 2257(Stabilizers);HIS 2012;ASP 2258
2hpaC ARG 3011;ARG 3015;ARG 3079;HIS 3257(Stabilizers);HIS 3012;ASP 3258
2hpaD ARG 4011;ARG 4015;ARG 4079;HIS 4257(Stabilizers);HIS 4012;ASP 4258

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig.2, Fig.3, p.141-142 3
[3]
Fig.4 2
[6]
p.111

References
[1]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8407898
Journal J Biol Chem
Year 1993
Volume 268
Pages 20744-6
Authors Lindqvist Y, Schneider G, Vihko P
Title Three-dimensional structure of rat acid phosphatase in complex with L(+)-tartrate.
Related PDB 1rpa
Related UniProtKB
[2]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8168503
Journal Eur J Biochem
Year 1994
Volume 221
Pages 139-142
Authors Lindqvist Y, Schneider G, Vihko P
Title Crystal structures of rat acid phosphatase complexed with the transition-state analogs vanadate and molybdate. Implications for the reaction mechanism.
Related PDB 1rpt
Related UniProtKB
[3]
Resource
Comments active site mutation, catalysis
Medline ID
PubMed ID 8132635
Journal J Biol Chem
Year 1994
Volume 269
Pages 8971-8
Authors Ostanin K, Saeed A, Van Etten RL
Title Heterologous expression of human prostatic acid phosphatase and site-directed mutagenesis of the enzyme active site.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-ray crystallography (2.9 Angstroms)
Medline ID
PubMed ID 9804805
Journal J Biol Chem
Year 1998
Volume 273
Pages 30406-9
Authors LaCount MW, Handy G, Lebioda L
Title Structural origins of L(+)-tartrate inhibition of human prostatic acid phosphatase.
Related PDB 2hpa
Related UniProtKB
[5]
Resource
Comments Improvement of catalytic efficiency by site-directed mutagenesis
Medline ID
PubMed ID 11051103
Journal Arch Biochem Biophys
Year 2000
Volume 382
Pages 105-12
Authors Rodriguez E, Wood ZA, Karplus PA, Lei XG
Title Site-directed mutagenesis improves catalytic efficiency and thermostability of Escherichia coli pH 2.5 acid phosphatase/phytase expressed in Pichia pastoris.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-ray crystallography (2.05 Angstroms)
Medline ID 20122624
PubMed ID 10655611
Journal Nat Struct Biol
Year 2000
Volume 7
Pages 108-13
Authors Lim D, Golovan S, Forsberg CW, Jia Z
Title Crystal structures of Escherichia coli phytase and its complex with phytate.
Related PDB 1dkl 1dkm 1dkn 1dko 1dkp 1dkq
Related UniProtKB
[7]
Resource
Comments X-ray crystallography (3.1 Angstroms)
Medline ID
PubMed ID 10639192
Journal Prostate
Year 2000
Volume 42
Pages 211-8
Authors Jakob CG, Lewinski K, Kuciel R, Ostrowski W, Lebioda L
Title Crystal structure of human prostatic acid phosphatase .
Related PDB
Related UniProtKB

Comments
According to the literature [2] and [3], His12 (of 1rpa/1rpt) acts as nucleophile, which attacks the phosphorous atom of the phosphate ester, whilst Asp258 protonates the leaving group. At the next stage, the deprotonated Asp258 abstracts proton from the water, which hydrolyzes the phosphorylated imidazole ring of His12 [2].
Moreover, the three positively charged arginine residues (Arg11, Arg15, Arg79) near His12 play an important role in the catalysis, as follows [2];
(1) The positive charged groups lower the pKa of the nucelophilic histidine (His12), so that the acidic phosphatase can function below pH 7.
(2) These groups will orient the phosphate group in a proper position so that the nucleophilic attack at the phosphorous atom can take place while the phosphorous-oxygen bond is cleaved.

Created Updated
2002-08-01 2009-02-26