View source for 4dhl


==Crystal structure of red kidney bean purple acid phosphatase in complex with Maybridge fragment MO07123==
<StructureSection load='4dhl' size='340' side='right'caption='[[4dhl]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4dhl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Phaseolus_vulgaris Phaseolus vulgaris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DHL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DHL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0K7:2-(4-METHYLPHENYL)-1,3-THIAZOLE-4-CARBOXYLIC+ACID'>0K7</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4dhl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dhl OCA], [https://pdbe.org/4dhl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dhl RCSB], [https://www.ebi.ac.uk/pdbsum/4dhl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dhl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PPAF_PHAVU PPAF_PHAVU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Purple acid phosphatases are metalloenzymes found in animals, plants and fungi. They possess a binuclear metal centre to catalyse the hydrolysis of phosphate esters and anhydrides under acidic conditions. In humans, elevated purple acid phosphatases levels in sera are correlated with the progression of osteoporosis and metabolic bone malignancies, making this enzyme a target for the development of new chemotherapeutics to treat bone-related illnesses. To date, little progress has been achieved towards the design of specific and potent inhibitors of this enzyme that have drug-like properties. Here, we have undertaken a fragment-based screening approach using a 500-compound library identifying three inhibitors of purple acid phosphatases with K(i) values in the 30-60 mum range. Ligand efficiency values are 0.39-0.44 kcal/mol per heavy atom. X-ray crystal structures of these compounds in complex with a plant purple acid phosphatases (2.3-2.7 A resolution) have been determined and show that all bind in the active site within contact of the binuclear centre. For one of these compounds, the phenyl ring is positioned within 3.5 A of the binuclear centre. Docking simulations indicate that the three compounds fit into the active site of human purple acid phosphatases. These studies open the way to the design of more potent and selective inhibitors of purple acid phosphatases that can be tested as anti-osteoporotic drug leads.

Identification of purple acid phosphatase inhibitors by fragment-based screening: promising new leads for osteoporosis therapeutics.,Feder D, Hussein WM, Clayton DJ, Kan MW, Schenk G, McGeary RP, Guddat LW Chem Biol Drug Des. 2012 Nov;80(5):665-74. doi: 10.1111/cbdd.12001. Epub 2012 Sep, 3. PMID:22943065<ref>PMID:22943065</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4dhl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acid phosphatase 3D structures|Acid phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Phaseolus vulgaris]]
[[Category: Clayton DJ]]
[[Category: Feder D]]
[[Category: Guddat LW]]
[[Category: Hussein WM]]
[[Category: McGeary R]]
[[Category: Schenk G]]