1nd6

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(New page: 200px<br /> <applet load="1nd6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nd6, resolution 2.40&Aring;" /> '''Crystal Structures ...)
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[[Image:1nd6.gif|left|200px]]<br />
 
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<applet load="1nd6" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1nd6, resolution 2.40&Aring;" />
 
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'''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'''<br />
 
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==Overview==
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==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==
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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.
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<StructureSection load='1nd6' size='340' side='right'caption='[[1nd6]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1nd6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ND6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ND6 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nd6 OCA], [https://pdbe.org/1nd6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nd6 RCSB], [https://www.ebi.ac.uk/pdbsum/1nd6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nd6 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PPAP_HUMAN 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.<ref>PMID:15280042</ref> <ref>PMID:18083097</ref> <ref>PMID:19403677</ref> <ref>PMID:20498373</ref> 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.<ref>PMID:15280042</ref> <ref>PMID:18083097</ref> <ref>PMID:19403677</ref> <ref>PMID:20498373</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nd/1nd6_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nd6 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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<ref>PMID:12525165</ref>
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1ND6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, PO4, GLY and 1PE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ND6 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12525165 12525165]
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</div>
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[[Category: Acid phosphatase]]
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<div class="pdbe-citations 1nd6" style="background-color:#fffaf0;"></div>
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[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: LaCount, M.W.]]
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[[Category: Lebioda, L.]]
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[[Category: Ortlund, E.]]
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[[Category: 1PE]]
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[[Category: GLY]]
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[[Category: NAG]]
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[[Category: PO4]]
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[[Category: inhibitor]]
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[[Category: pap]]
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[[Category: phosphate]]
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[[Category: prostate]]
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[[Category: prostatic acid phosphatase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:20:33 2007''
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==See Also==
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*[[Acid phosphatase 3D structures|Acid phosphatase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: LaCount MW]]
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[[Category: Lebioda L]]
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[[Category: Ortlund E]]

Current revision

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

PDB ID 1nd6

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