1md2

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[[Image:1md2.gif|left|200px]]<br /><applet load="1md2" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1md2, resolution 1.45&Aring;" />
 
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'''CHOLERA TOXIN B-PENTAMER WITH DECAVALENT LIGAND BMSC-0013'''<br />
 
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==Overview==
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==CHOLERA TOXIN B-PENTAMER WITH DECAVALENT LIGAND BMSC-0013==
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The structure-based design of multivalent ligands offers an attractive strategy toward high affinity protein inhibitors. The spatial arrangement of the receptor-binding sites of cholera toxin, the causative agent of the severe diarrheal disease cholera and a member of the AB(5) bacterial toxin family, provides the opportunity of designing branched multivalent ligands with 5-fold symmetry. Our modular synthesis enabled the construction of a family of complex ligands with five flexible arms each ending with a bivalent ligand. The largest of these ligands has a molecular weight of 10.6 kDa. These ligands are capable of simultaneously binding to two toxin B pentamer molecules with high affinity, thus blocking the receptor-binding process of cholera toxin. A more than million-fold improvement over the monovalent ligand in inhibitory power was achieved with the best branched decavalent ligand. This is better than the improvement observed earlier for the corresponding nonbranched pentavalent ligand. Dynamic light scattering studies demonstrate the formation of concentration-dependent unique 1:1 and 1:2 ligand/toxin complexes in solution with no sign of nonspecific aggregation. This is in complete agreement with a crystal structure of the branched multivalent ligand/toxin B pentamer complex solved at 1.45 A resolution that shows the specific 1:2 ligand/toxin complex formation in the solid state. These results reiterate the power of the structure-based design of multivalent protein ligands as a general strategy for achieving high affinity and potent inhibition.
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<StructureSection load='1md2' size='340' side='right'caption='[[1md2]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1md2]] 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=1MD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MD2 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=233:[5-(3,4,5-TRIHYDROXY-6-HYDROXYMETHYL-TETRAHYDRO-PYRAN-2-YLCARBAMOYL)-PENTYL]-CARBAMIC+ACID+METHYL+ESTER'>233</scene>, <scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene>, <scene name='pdbligand=CYN:CYANIDE+ION'>CYN</scene>, <scene name='pdbligand=SQ:3-ETHYLAMINO-4-METHYLAMINO-CYCLOBUTANE-1,2-DIONE'>SQ</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1md2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1md2 OCA], [https://pdbe.org/1md2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1md2 RCSB], [https://www.ebi.ac.uk/pdbsum/1md2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1md2 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[https://www.uniprot.org/uniprot/CHTB_VIBCH CHTB_VIBCH]] The B subunit pentameric ring directs the A subunit to its target by binding to the GM1 gangliosides present on the surface of the intestinal epithelial cells. It can bind five GM1 gangliosides. It has no toxic activity by itself.
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==About this Structure==
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==See Also==
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1MD2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae] with <scene name='pdbligand=CYN:'>CYN</scene>, <scene name='pdbligand=S:'>S</scene>, <scene name='pdbligand=233:'>233</scene> and <scene name='pdbligand=SQ:'>SQ</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MD2 OCA].
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*[[Cholera toxin 3D structures|Cholera toxin 3D structures]]
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*[[User:David Solfiell/sandbox 1|User:David Solfiell/sandbox 1]]
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==Reference==
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__TOC__
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Solution and crystallographic studies of branched multivalent ligands that inhibit the receptor-binding of cholera toxin., Zhang Z, Merritt EA, Ahn M, Roach C, Hou Z, Verlinde CL, Hol WG, Fan E, J Am Chem Soc. 2002 Nov 6;124(44):12991-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12405825 12405825]
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</StructureSection>
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[[Category: Single protein]]
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[[Category: Large Structures]]
[[Category: Vibrio cholerae]]
[[Category: Vibrio cholerae]]
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[[Category: Ahn, M.]]
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[[Category: Ahn M]]
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[[Category: Fan, E.]]
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[[Category: Fan E]]
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[[Category: Hol, W G.J.]]
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[[Category: Hol WGJ]]
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[[Category: Merritt, E A.]]
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[[Category: Merritt EA]]
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[[Category: Roach, C.]]
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[[Category: Roach C]]
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[[Category: Zhang, Z.]]
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[[Category: Zhang Z]]
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[[Category: 233]]
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[[Category: CYN]]
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[[Category: S]]
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[[Category: SQ]]
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[[Category: multivalent inhibitor toxin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:54:03 2008''
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Current revision

CHOLERA TOXIN B-PENTAMER WITH DECAVALENT LIGAND BMSC-0013

PDB ID 1md2

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