| Structural highlights
1nd5 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.9Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
PPAP_HUMAN A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins. Has lipid phosphatase activity and inactivates lysophosphatidic acid in seminal plasma.[1] [2] [3] [4] Isoform 2: the cellular form also has ecto-5'-nucleotidase activity in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP which acts as a pain suppressor. Acts as a tumor suppressor of prostate cancer through dephosphorylation of ERBB2 and deactivation of MAPK-mediated signaling.[5] [6] [7] [8]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The X-ray crystal structure of human prostatic acid phosphatase (PAP) in complex with a phosphate ion has been determined at 2.4 A resolution. This structure offers a snapshot of the final intermediate in the catalytic mechanism and does not support the role of Asp 258 as a proton donor in catalysis. A total of eight hydrogen bonds serve to strongly bind the phosphate ion within the active site. Bound PEG molecules from the crystallization matrix have allowed the identification of a channel within the molecule that likely plays a role in molecular recognition and in macromolecular substrate selectivity. Additionally, the structure of PAP in complex with a phosphate derivative, alpha-benzylaminobenzylphosphonic acid, a potent inhibitor (IC(50) = 4 nM), has been determined to 2.9 A resolution. This structure gives new insight into the determinants of binding hydrophobic ligands within the active site and allows us to explain PAP's preference for aromatic substrates.
Crystal structures of human prostatic acid phosphatase in complex with a phosphate ion and alpha-benzylaminobenzylphosphonic acid update the mechanistic picture and offer new insights into inhibitor design.,Ortlund E, LaCount MW, Lebioda L Biochemistry. 2003 Jan 21;42(2):383-9. PMID:12525165[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tanaka M, Kishi Y, Takanezawa Y, Kakehi Y, Aoki J, Arai H. Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma. FEBS Lett. 2004 Jul 30;571(1-3):197-204. PMID:15280042 doi:10.1016/j.febslet.2004.06.083
- ↑ Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, Gimenez-Gallego G, Sanchez PC, Fowler DM, Koulov A, Kelly JW, Mothes W, Grivel JC, Margolis L, Keppler OT, Forssmann WG, Kirchhoff F. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell. 2007 Dec 14;131(6):1059-71. PMID:18083097 doi:10.1016/j.cell.2007.10.014
- ↑ Hong S, Klein EA, Das Gupta J, Hanke K, Weight CJ, Nguyen C, Gaughan C, Kim KA, Bannert N, Kirchhoff F, Munch J, Silverman RH. Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer. J Virol. 2009 Jul;83(14):6995-7003. doi: 10.1128/JVI.00268-09. Epub 2009 Apr 29. PMID:19403677 doi:10.1128/JVI.00268-09
- ↑ Chuang TD, Chen SJ, Lin FF, Veeramani S, Kumar S, Batra SK, Tu Y, Lin MF. Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth. J Biol Chem. 2010 Jul 30;285(31):23598-606. doi: 10.1074/jbc.M109.098301. Epub, 2010 May 24. PMID:20498373 doi:10.1074/jbc.M109.098301
- ↑ Tanaka M, Kishi Y, Takanezawa Y, Kakehi Y, Aoki J, Arai H. Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma. FEBS Lett. 2004 Jul 30;571(1-3):197-204. PMID:15280042 doi:10.1016/j.febslet.2004.06.083
- ↑ Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, Gimenez-Gallego G, Sanchez PC, Fowler DM, Koulov A, Kelly JW, Mothes W, Grivel JC, Margolis L, Keppler OT, Forssmann WG, Kirchhoff F. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell. 2007 Dec 14;131(6):1059-71. PMID:18083097 doi:10.1016/j.cell.2007.10.014
- ↑ Hong S, Klein EA, Das Gupta J, Hanke K, Weight CJ, Nguyen C, Gaughan C, Kim KA, Bannert N, Kirchhoff F, Munch J, Silverman RH. Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer. J Virol. 2009 Jul;83(14):6995-7003. doi: 10.1128/JVI.00268-09. Epub 2009 Apr 29. PMID:19403677 doi:10.1128/JVI.00268-09
- ↑ Chuang TD, Chen SJ, Lin FF, Veeramani S, Kumar S, Batra SK, Tu Y, Lin MF. Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth. J Biol Chem. 2010 Jul 30;285(31):23598-606. doi: 10.1074/jbc.M109.098301. Epub, 2010 May 24. PMID:20498373 doi:10.1074/jbc.M109.098301
- ↑ Ortlund E, LaCount MW, Lebioda L. Crystal structures of human prostatic acid phosphatase in complex with a phosphate ion and alpha-benzylaminobenzylphosphonic acid update the mechanistic picture and offer new insights into inhibitor design. Biochemistry. 2003 Jan 21;42(2):383-9. PMID:12525165 doi:10.1021/bi0265067
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