4jfw
From Proteopedia
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| - | + | ==Crystal structure of a bacterial fucosidase with iminosugar inhibitor (2S,3S,4R,5S)-2-[N-(propylferrocene)]aminoethyl-5-methylpyrrolidine-3,4-diol== | |
| - | + | <StructureSection load='4jfw' size='340' side='right' caption='[[4jfw]], [[Resolution|resolution]] 2.10Å' scene=''> | |
| - | { | + | == Structural highlights == |
| + | <table><tr><td colspan='2'>[[4jfw]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bactn Bactn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JFW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JFW FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H58:(3ALPHA)-[3-({2-[(2S,3S,4R,5S)-3,4-DIHYDROXY-5-METHYLPYRROLIDIN-2-YL]ETHYL}AMINO)PROPYL]FERROCENE'>H58</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br> | ||
| + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wvv|2wvv]], [[4j27|4j27]], [[4j28|4j28]], [[4jfs|4jfs]], [[4jft|4jft]], [[4jfu|4jfu]], [[4jfv|4jfv]]</td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jfw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jfw RCSB], [http://www.ebi.ac.uk/pdbsum/4jfw PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | <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®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Bactn]] | ||
[[Category: Davies, G J.]] | [[Category: Davies, G J.]] | ||
[[Category: Wright, D W.]] | [[Category: Wright, D W.]] | ||
[[Category: Alpha-l-fucosidase]] | [[Category: Alpha-l-fucosidase]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 06:25, 2 July 2014
Crystal structure of a bacterial fucosidase with iminosugar inhibitor (2S,3S,4R,5S)-2-[N-(propylferrocene)]aminoethyl-5-methylpyrrolidine-3,4-diol
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