This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2hpa

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 23:45, 10 September 2015

STRUCTURAL ORIGINS OF L(+)-TARTRATE INHIBITION OF HUMAN PROSTATIC ACID PHOSPHATASE

Structural highlights

2hpa 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.
Ligands:	, , , ,
Activity:	Acid phosphatase, with EC number 3.1.3.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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

Acid phosphatase activity in the blood serum is usually separated into tartrate-resistant and tartrate-refractory, which is reported as the prostatic acid phosphatase level. Human prostatic acid phosphatase crystals soaked in N-propyl-L-tartramate were used to collect x-ray diffraction data to 2.9 A resolution under cryogenic conditions. Positive difference electron density, corresponding to the inhibitor, was found. The quality of the electron density maps clearly shows the orientation of the carboxylate and N-propyl-substituted amide groups. The hydroxyl group attached to C3 forms two crucial hydrogen bonds with Arg-79 and His-257. Previous crystallographic studies compiled on the tartrate-rat prostatic acid phosphatase binary complex (Lindqvist, Y., Schneider, G., and Vihko, P. (1993) J. Biol. Chem. 268, 20744-20746) erroneously positioned D-tartrate into the active site. Modeling studies have shown that the C3 hydroxyl group on the D(-)-stereoisomer of tartrate, which does not significantly inhibit prostatic acid phosphatase, does not form strong hydrogen bonds with Arg-79 or His-257. The structure of human prostatic acid phosphatase, noncovalently bound in N-propyl-L-tartramate, is used to develop inhibitors with higher specificity and potency than L(+)-tartrate.

Structural origins of L(+)-tartrate inhibition of human prostatic acid phosphatase.,LaCount MW, Handy G, Lebioda L J Biol Chem. 1998 Nov 13;273(46):30406-9. PMID:9804805^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ LaCount MW, Handy G, Lebioda L. Structural origins of L(+)-tartrate inhibition of human prostatic acid phosphatase. J Biol Chem. 1998 Nov 13;273(46):30406-9. PMID:9804805

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2hpa"

@@ Line 5: / Line 5: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=PT3:N-PROPYL-TARTRAMIC+ACID'>PT3</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acid_phosphatase Acid phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.2 3.1.3.2] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hpa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hpa RCSB], [http://www.ebi.ac.uk/pdbsum/2hpa PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hpa OCA], [http://pdbe.org/2hpa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hpa RCSB], [http://www.ebi.ac.uk/pdbsum/2hpa PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 27: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2hpa" style="background-color:#fffaf0;"></div>
 ==See Also==

2hpa

From Proteopedia

Revision as of 23:45, 10 September 2015

STRUCTURAL ORIGINS OF L(+)-TARTRATE INHIBITION OF HUMAN PROSTATIC ACID PHOSPHATASE

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox