1RCV

Cholera Toxin B-Pentamer Complexed With Bivalent Nitrophenol-Galactoside Ligand BV1

Summary for 1RCV

• Entry DOI: 10.2210/pdb1rcv/pdb
• Related: 1RD9 1RDP 1RF2
• Descriptor: cholera toxin B protein (CTB), [3-(4-{3-[3-NITRO-5-(GALACTOPYRANOSYLOXY)-BENZOYLAMINO]-PROPYL}-PIPERAZIN-1-YL)-PROPYLAMINO] -2-(3-{4-[3-(3-NITRO-5-[GALACTOPYRANOSYLOXY]-BENZOYLAMINO)-PROPYL]-PIPERAZIN-1-YL} -PROPYL-AMINO)-3,4-DIOXO-CYCLOBUTENE (3 entities in total)
• Functional Keywords: bivalent, cholera, toxin, pentamer, complex
• Biological source: Vibrio cholerae
• Cellular location: Secreted: P01556
• Total number of polymer chains: 5
• Total formula weight: 63782.14

Authors

Pickens, J.C.,Mitchell, D.D.,Liu, J.,Tan, X.,Zhang, Z.,Verlinde, C.L.,Hol, W.G.,Fan, E. (deposition date: 2003-11-04, release date: 2004-10-26, Last modification date: 2024-10-30)

Primary citation

Pickens, J.C.,Mitchell, D.D.,Liu, J.,Tan, X.,Zhang, Z.,Verlinde, C.L.,Hol, W.G.,Fan, E.
Nonspanning bivalent ligands as improved surface receptor binding inhibitors of the cholera toxin B pentamer.
Chem.Biol., 11:1205-1215, 2004

PubMed Abstract: A series of bivalent ligands of varying length were synthesized to inhibit the receptor-binding process of cholera toxin. Competitive surface receptor binding assays showed that significant potency gains relative to the constituent monovalent ligands were achieved independently from the ability of the extended bivalent ligands to span binding sites within the toxin pentamer. Several models that could account for the unexpected improvement in IC(50) values are examined, taking into account crystallographic analysis of each ligand in complex with the toxin pentamer. Evidence is presented that steric blocking at the receptor binding surface may play a role. The results of our study suggest that the use of relatively short, "nonspanning" bivalent ligands, or monovalent ligands of similar topology and bulk may be an effective way of blocking the interaction of multimeric proteins with their cell surface receptors.

PubMed: 15380181
DOI: 10.1016/j.chembiol.2004.06.008

Experimental method

X-RAY DIFFRACTION (1.6 Å)