View source for 7ov8


==Crystal structure of pig purple acid phosphatase in complex with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and glycerol==
<StructureSection load='7ov8' size='340' side='right'caption='[[7ov8]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OV8 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7ov8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ov8 OCA], [https://pdbe.org/7ov8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ov8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ov8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ov8 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Metallohydrolases form a large group of enzymes that have fundamental importance in a broad range of biological functions. Among them, the purple acid phosphatases (PAPs) have gained attention due to their crucial role in the acquisition and use of phosphate by plants and also as a promising target for novel treatments of bone-related disorders and cancer. To date, no crystal structure of a mammalian PAP with drug-like molecules bound near the active site is available. Herein, we used a fragment-based design approach using structures of a mammalian PAP in complex with the Maybridge(TM) fragment CC063346, the amino acid L-glutamine and the buffer molecule HEPES, as well as various solvent molecules to guide the design of highly potent and efficient mammalian PAP inhibitors. These inhibitors have improved aqueous solubility when compared to the clinically most promising PAP inhibitors available to date. Furthermore, drug-like fragments bound in newly discovered binding sites mapped out additional scaffolds for further inhibitor discovery, as well as scaffolds for the design of inhibitors with novel modes of action.

Rational Design of Potent Inhibitors of a Metallohydrolase Using a Fragment-Based Approach.,Feder D, Mohd-Pahmi SH, Hussein WM, Guddat LW, McGeary RP, Schenk G ChemMedChem. 2021 Nov 5;16(21):3342-3359. doi: 10.1002/cmdc.202100486. Epub 2021 , Sep 1. PMID:34331400<ref>PMID:34331400</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ov8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acid phosphatase 3D structures|Acid phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Feder D]]
[[Category: Guddat LW]]
[[Category: McGeary RP]]
[[Category: Schenk G]]