1md2 | pdb_00001md2

CHOLERA TOXIN B-PENTAMER WITH DECAVALENT LIGAND BMSC-0013

spinqualitylabelsall models 1md2, resolution 1.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1md2 is a 5 chain structure with sequence from "bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 233, CYN, SQ NonStd Res: CSS Related: 3chb, 1llr Gene: CTXB ("Bacillo virgola del Koch" Trevisan 1884) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Publication Abstract from PubMed 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. 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:12405825 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cholera toxin User:David Solfiell/sandbox 1

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