View source for 1pzj


==Cholera Toxin B-Pentamer Complexed With Nitrophenyl Galactoside 5==
<StructureSection load='1pzj' size='340' side='right'caption='[[1pzj]], [[Resolution|resolution]] 1.46&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pzj]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PZJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PZJ 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]] 1.46&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=15B:N-{3-[4-(3-AMINO-PROPYL)-PIPERAZIN-1-YL]-PROPYL}-3-NITRO-5-(GALACTOPYRANOSYL)-BETA-BENZAMIDE'>15B</scene>, <scene name='pdbligand=J15:N-{3-[4-(3-AMINO-PROPYL)-PIPERAZIN-1-YL]-PROPYL}-3-NITRO-5-(GALACTOPYRANOSYL)-ALPHA-BENZAMIDE'>J15</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=1pzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pzj OCA], [https://pdbe.org/1pzj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pzj RCSB], [https://www.ebi.ac.uk/pdbsum/1pzj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pzj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q57193_VIBCL Q57193_VIBCL] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
With the aim of developing high-affinity mono and multivalent antagonists of cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) we are using the galactose portion of the natural receptor ganglioside GM1 as an anchoring fragment in structure-based inhibitor design efforts. In order to establish a better structure-activity relationship for guiding these studies, we designed and prepared a small focused library of twenty 3,5-substituted phenylgalactosides based on two previous leads. The compounds were tested for their ability to block CTB(5) binding to immobilized ganglioside receptor and compared to the two previous leads. The crystal structures of the most promising compounds bound to either CTB(5) or LTB(5) were then determined in order to understand the basis for affinity differences. The most potent new compound yielded a six-fold improvement over our benchmark lead m-nitrophenyl-alpha-d-galactopyranoside (MNPG), and a two-fold improvement in IC(50) over a newer MNPG derivative. These results support the notion that the m-nitrophenyl moiety of MNPG and its derivatives is an important element to retain in future optimization efforts. Additionally, a consensus binding-pocket for the alkylmorpholine or piperazine moiety present in all of the designed antagonists was established as an important area of the GM1 binding site to target in future work.

3,5-Substituted phenyl galactosides as leads in designing effective cholera toxin antagonists; synthesis and crystallographic studies.,Mitchell DD, Pickens JC, Korotkov K, Fan E, Hol WG Bioorg Med Chem. 2004 Mar 1;12(5):907-20. PMID:14980603<ref>PMID:14980603</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1pzj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cholera toxin 3D structures|Cholera toxin 3D structures]]
*[[User:David Solfiell/sandbox 1|User:David Solfiell/sandbox 1]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Vibrio cholerae]]
[[Category: Fan E]]
[[Category: Hol WGJ]]
[[Category: Korotkov K]]
[[Category: Mitchell DD]]
[[Category: Pickens JC]]