View source for 5fue


==Crystal structure of Schistosoma mansoni HDAC8 complexed with 3- benzamido-benzohydroxamate==
<StructureSection load='5fue' size='340' side='right'caption='[[5fue]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5fue]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FUE 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]] 2.199&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=UV4:3-(BENZOYLAMINO)-N-OXOBENZAMIDE'>UV4</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=5fue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fue OCA], [https://pdbe.org/5fue PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fue RCSB], [https://www.ebi.ac.uk/pdbsum/5fue PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fue ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A5H660_SCHMA A5H660_SCHMA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (1 and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.

Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis.,Heimburg T, Chakrabarti A, Lancelot J, Marek M, Melesina J, Hauser AT, Shaik TB, Duclaud S, Robaa D, Erdmann F, Schmidt M, Romier C, Pierce RJ, Jung M, Sippl W J Med Chem. 2016 Mar 24;59(6):2423-35. doi: 10.1021/acs.jmedchem.5b01478. Epub, 2016 Mar 14. PMID:26937828<ref>PMID:26937828</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5fue" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Schistosoma mansoni]]
[[Category: Marek M]]
[[Category: Romier C]]