View source for 1pzi


==Heat-Labile Enterotoxin B-Pentamer Complexed With Nitrophenyl Galactoside 2a==
<StructureSection load='1pzi' size='340' side='right'caption='[[1pzi]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pzi]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PZI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PZI 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]] 1.99&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1DM:N-(2-MORPHOLIN-4-YL-1-MORPHOLIN-4-YLMETHYL-ETHYL)-3-NITRO-5-(3,4,5-TRIHYDROXY-6-HYDROXYMETHYL-TETRAHYDRO-PYRAN-2-YLOXY)-BENZAMIDE'>1DM</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=1pzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pzi OCA], [https://pdbe.org/1pzi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pzi RCSB], [https://www.ebi.ac.uk/pdbsum/1pzi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pzi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ELBP_ECOLX ELBP_ECOLX] The biological activity of the toxin is produced by the A chain, which activates intracellular adenyl cyclase.
<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 1pzi" 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: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Fan E]]
[[Category: Hol WGJ]]
[[Category: Korotkov K]]
[[Category: Mitchell DD]]
[[Category: Pickens JC]]