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| Enzyme Name | | UniProtKB | KEGG |
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| P80366 |
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| Protein name | Fe(3+)-Zn(2+) purple acid phosphatase (PAP) (EC 3.1.3.2) (Iron | acid phosphataseacid phosphomonoesterasephosphomonoesteraseglycerophosphataseacid monophosphataseacid phosphohydrolaseacid phosphomonoester hydrolaseuteroferrinacid nucleoside diphosphate phosphataseorthophosphoric-monoester phosphohydrolase (acid optimum) |
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| Synonyms | III)-zinc(II) purple acid phosphatase |
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| Pfam | PF00149 (Metallophos)
PF14008 (Metallophos_C)
[Graphical view]
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| KEGG pathways | | MAP code | Pathways |
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| MAP00361 | gamma-Hexachlorocyclohexane degradation | | MAP00740 | Riboflavin metabolism |
| UniProtKB:Accession Number | P80366 |
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| Entry name | PPAF_PHAVU |
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| Activity | A phosphate monoester + H(2)O = an alcohol + phosphate. |
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| Subunit | Homodimer, disulfide-linked. |
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| Subcellular location | Secreted. |
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| Cofactor | Binds 1 iron ion per subunit.,Binds 1 zinc ion per subunit. |
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| References for Catalytic Mechanism | | References | Sections | No. of steps in catalysis |
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| [5] | p.1490-1491 |
| | [6] | Fig.6, p.740-744 | 3 | | [11] | p.203-208 |
| | [13] | p.9923-9924, Scheme 3 |
| | [15] | Fig.8, p.143-144 | 2 | | [20] | p.5643 |
|
| references | | [1] |
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| PubMed ID | 1648483 |
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| Journal | Eur J Biochem |
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| Year | 1991 |
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| Volume | 199 |
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| Pages | 105-13 |
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| Authors | Dietrich M, Munstermann D, Suerbaum H, Witzel H |
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| Title | Purple acid phosphatase from bovine spleen. Interactions at the active site in relation to the reaction mechanism. |
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| [2] |
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| PubMed ID | 1332769 |
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| Journal | Biochemistry |
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| Year | 1992 |
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| Volume | 31 |
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| Pages | 11731-9 |
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| Authors | Crans DC, Simone CM, Holz RC, Que L Jr |
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| Title | Interaction of porcine uterine fluid purple acid phosphatase with vanadate and vanadyl cation. |
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| [3] |
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| PubMed ID | 7821667 |
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| Journal | Biochem Soc Trans |
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| Year | 1994 |
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| Volume | 22 |
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| Pages | 700-4 |
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| Authors | Wilkins PC, Dalton H |
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| Title | Variations on a theme of Fe-O-Fe proteins. |
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| [4] |
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| PubMed ID | 7771777 |
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| Journal | Arch Biochem Biophys |
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| Year | 1995 |
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| Volume | 319 |
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| Pages | 133-41 |
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| Authors | Wynne CJ, Hamilton SE, Dionysius DA, Beck JL, de Jersey J |
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| Title | Studies on the catalytic mechanism of pig purple acid phosphatase. |
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| [5] |
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| PubMed ID | 7770774 |
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| Journal | Science |
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| Year | 1995 |
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| Volume | 268 |
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| Pages | 1489-92 |
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| Authors | Strater N, Klabunde T, Tucker P, Witzel H, Krebs B |
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| Title | Crystal structure of a purple acid phosphatase containing a dinuclear Fe(III)-Zn(II) active site. |
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| [6] |
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| Comments | X-ray crystallography |
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| Medline ID | 96275658 |
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| PubMed ID | 8683579 |
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| Journal | J Mol Biol |
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| Year | 1996 |
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| Volume | 259 |
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| Pages | 737-48 |
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| Authors | Klabunde T, Strater N, Frohlich R, Witzel H, Krebs B |
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| Title | Mechanism of Fe(III)-Zn(II) purple acid phosphatase based on crystal structures. |
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| Related PDB | 1kbp,3kbp,4kbp |
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| Related UniProtKB | P80366 |
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| [7] |
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| PubMed ID | 9020859 |
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| Journal | Biochem J |
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| Year | 1997 |
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| Volume | 321 |
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| Pages | 305-11 |
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| Authors | Ek-Rylander B, Barkhem T, Ljusberg J, Ohman L, Andersson KK, Andersson G |
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| Title | Comparative studies of rat recombinant purple acid phosphatase and bone tartrate-resistant acid phosphatase. |
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| [8] |
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| PubMed ID | 9169589 |
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| Journal | Biochem J |
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| Year | 1997 |
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| Volume | 323 |
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| Pages | 593-6 |
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| Authors | Battistuzzi G, Dietrich M, Locke R, Witzel H |
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| Title | Evidence 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. |
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| [9] |
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| PubMed ID | 9698368 |
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| Journal | Biochemistry |
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| Year | 1998 |
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| Volume | 37 |
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| Pages | 11223-31 |
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| Authors | Merkx M, Averill BA |
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| Title | The activity of oxidized bovine spleen purple acid phosphatase is due to an Fe(III)Zn(II) 'impurity'. |
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| [10] |
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| PubMed ID | 10376348 |
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| Journal | J Inorg Biochem |
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| Year | 1999 |
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| Volume | 73 |
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| Pages | 245-52 |
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| Authors | Beck JL, Durack MC, Hamilton SE, de Jersey J |
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| Title | Irreversible inactivation of purple acid phosphatase by hydrogen peroxide and ascorbate. |
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| [11] |
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| Comments | X-ray crystallography (2.7 Angstroms) |
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| PubMed ID | 10388567 |
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| Journal | J Mol Biol |
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| Year | 1999 |
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| Volume | 290 |
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| Pages | 201-11 |
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| Authors | Uppenberg J, Lindqvist F, Svensson C, Ek-Rylander B, Andersson G |
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| Title | Crystal structure of a mammalian purple acid phosphatase. |
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| Related PDB | 1qfc |
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| [12] |
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| Comments | X-ray crystallography (1.55 Angstroms) |
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| PubMed ID | 10425678 |
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| Journal | Structure Fold Des |
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| Year | 1999 |
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| Volume | 7 |
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| Pages | 757-67 |
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| Authors | Guddat LW, McAlpine AS, Hume D, Hamilton S, de Jersey J, Martin JL |
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| Title | Crystal structure of mammalian purple acid phosphatase. |
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| Related PDB | 1ute |
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| [13] |
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| PubMed ID | 10433698 |
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| Journal | Biochemistry |
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| Year | 1999 |
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| Volume | 38 |
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| Pages | 9914-25 |
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| Authors | Merkx M, Pinkse MW, Averill BA |
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| Title | Evidence for nonbridged coordination of p-nitrophenyl phosphate to the dinuclear Fe(III)-M(II) center in bovine spleen purple acid phosphatase during enzymatic turnover. |
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| [14] |
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| PubMed ID | 10433699 |
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| Journal | Biochemistry |
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| Year | 1999 |
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| Volume | 38 |
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| Pages | 9926-36 |
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| Authors | Pinkse MW, Merkx M, Averill BA |
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| Title | Fluoride 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. |
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| [15] |
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| Comments | X-ray crystallography (2.2 Angstroms) |
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| PubMed ID | 10438611 |
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| Journal | J Mol Biol |
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| Year | 1999 |
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| Volume | 291 |
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| Pages | 135-47 |
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| Authors | Lindqvist Y, Johansson E, Kaija H, Vihko P, Schneider G |
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| Title | Three-dimensional structure of a mammalian purple acid phosphatase at 2.2 A resolution with a mu-(hydr)oxo bridged di-iron center. |
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| Related PDB | 1qhw |
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| [16] |
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| PubMed ID | 11278566 |
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| Journal | J Biol Chem |
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| Year | 2001 |
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| Volume | 276 |
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| Pages | 19084-8 |
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| Authors | Schenk G, Boutchard CL, Carrington LE, Noble CJ, Moubaraki B, Murray KS, de Jersey J, Hanson GR, Hamilton S |
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| Title | A purple acid phosphatase from sweet potato contains an antiferromagnetically coupled binuclear Fe-Mn center. |
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| [17] |
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| PubMed ID | 11491293 |
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| Journal | J Mol Biol |
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| Year | 2001 |
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| Volume | 309 |
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| Pages | 239-54 |
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| Authors | Knofel T, Strater N |
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| Title | Mechanism of hydrolysis of phosphate esters by the dimetal center of 5'-nucleotidase based on crystal structures. |
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| [18] |
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| PubMed ID | 11560512 |
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| Journal | Biochemistry |
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| Year | 2001 |
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| Volume | 40 |
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| Pages | 11614-22 |
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| Authors | Funhoff EG, Ljusberg J, Wang Y, Andersson G, Averill BA |
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| Title | Mutational analysis of the interaction between active site residues and the loop region in mammalian purple acid phosphatases. |
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| [19] |
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| PubMed ID | 11828464 |
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| Journal | Chembiochem |
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| Year | 2001 |
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| Volume | 2 |
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| Pages | 355-63 |
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| Authors | Funhoff EG, Klaassen CH, Samyn B, Van Beeumen J, Averill BA |
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| Title | The highly exposed loop region in mammalian purple acid phosphatase controls the catalytic activity. |
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| [20] |
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| PubMed ID | 12401063 |
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| Journal | Inorg Chem |
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| Year | 2002 |
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| Volume | 41 |
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| Pages | 5641-3 |
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| Authors | Lanznaster M, Neves A, Bortoluzzi AJ, Szpoganicz B, Schwingel E |
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| Title | New 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. |
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| [21] |
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| PubMed ID | 12440878 |
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| Journal | J Am Chem Soc |
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| Year | 2002 |
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| Volume | 124 |
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| Pages | 13974-5 |
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| Authors | Dikiy A, Funhoff EG, Averill BA, Ciurli S |
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| Title | New insights into the mechanism of purple acid phosphatase through (1)H NMR spectroscopy of the recombinant human enzyme. |
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| [22] |
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| PubMed ID | 12484780 |
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| Journal | Biochemistry |
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| Year | 2002 |
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| Volume | 41 |
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| Pages | 15404-9 |
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| Authors | Reiter TA, Reiter NJ, Rusnak F |
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| Title | Mn2+ is a native metal ion activator for bacteriophage lambda protein phosphatase. |
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| [23] |
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| PubMed ID | 12693232 |
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| Journal | Inorg Chem |
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| Year | 2003 |
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| Volume | 42 |
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| Pages | 499-507 |
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| Authors | Verge F, Lebrun C, Fontecave M, Menage S |
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| Title | Hydrolysis of phosphodiesters by diiron complexes: design of nonequivalent iron sites in purple acid phosphatase models. |
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| 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]).
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| created | updated |
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| 2002-07-09 | 2009-02-26 |
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