View source for 4jfs


==Crystal structure of a bacterial fucosidase with iminosugar inhibitor 4-epi-(+)-Codonopsinine==
<StructureSection load='4jfs' size='340' side='right'caption='[[4jfs]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4jfs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron_VPI-5482 Bacteroides thetaiotaomicron VPI-5482]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JFS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JFS 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=16Z:(2S,3S,4R,5S)-2-(4-METHOXYPHENYL)-1,5-DIMETHYLPYRROLIDINE-3,4-DIOL'>16Z</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4jfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jfs OCA], [https://pdbe.org/4jfs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jfs RCSB], [https://www.ebi.ac.uk/pdbsum/4jfs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jfs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8A3I4_BACTN Q8A3I4_BACTN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Enhanced metabolism of fucose through fucosidase overexpression is a signature of some cancer types, thus suggesting that fucosidase-targetted ligands could play the role of drug-delivery vectors. Herein, we describe the synthesis of a new series of pyrrolidine-ferrocene conjugates, consisting of a L-fuco-configured dihydroxypyrrolidine as the fucosidase ligand armed with a cytotoxic ferrocenylamine moeity. Three-dimensional structures of several of these fucosidase inhibitors reveal transition-state-mimicking (3)E conformations. Elaboration with the ferrocenyl moiety results in sub-micromolar inhibitors of both bovine and bacterial fucosidases, with the 3D structure of the latter revealing electron density indicative of highly mobile alkylferrocene compounds. The best compounds show a strong antiproliferative effect, with up to 100% inhibition of the proliferation of MDA-MB-231 cancer cells at 50 muM.

alpha-L-fucosidase inhibition by pyrrolidine-ferrocene hybrids: rationalization of ligand-binding properties by structural studies.,Hottin A, Wright DW, Steenackers A, Delannoy P, Dubar F, Biot C, Davies GJ, Behr JB Chemistry. 2013 Jul 15;19(29):9526-33. doi: 10.1002/chem.201301001. Epub 2013 Jun, 5. PMID:23740878<ref>PMID:23740878</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4jfs" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacteroides thetaiotaomicron VPI-5482]]
[[Category: Large Structures]]
[[Category: Davies GJ]]
[[Category: Wright DW]]