PDBsum entry 1rf2

Toxin

PDB id: 1rf2

Contents

Protein chains

103 a.a.

Ligands

BV4 ×5

TRS

PGE

Waters ×498

PDB id:

1rf2

Name:

Toxin

Title:

Cholera toxin b-pentamer complexed with bivalent nitrophenol- galactoside ligand bv4

Structure:

Cholera toxin b protein (ctb). Chain: d, e, f, g, h. Engineered: yes

Source:

Vibrio cholerae. Organism_taxid: 666. Gene: ctxb. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Pentamer (from PQS)

Resolution:

1.35Å R-factor: 0.134 R-free: 0.174

Authors:

J.C.Pickens,D.D.Mitchell,J.Liu,X.Tan,Z.Zhang,C.L.Verlinde,W.G.Hol, E.Fan

Key ref:

J.C.Pickens et al. (2004). Nonspanning bivalent ligands as improved surface receptor binding inhibitors of the cholera toxin B pentamer. Chem Biol, 11, 1205-1215. PubMed id: 15380181 DOI: 10.1016/j.chembiol.2004.06.008

Date:

07-Nov-03 Release date: 26-Oct-04

Protein chains

P01556  (CHTB_VIBCH) -  Cholera enterotoxin subunit B from Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)

Seq: 124 a.a.

Struc: 103 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.chembiol.2004.06.008

Chem Biol 11:1205-1215 (2004)

PubMed id: 15380181

Nonspanning bivalent ligands as improved surface receptor binding inhibitors of the cholera toxin B pentamer.

J.C.Pickens, D.D.Mitchell, J.Liu, X.Tan, Z.Zhang, C.L.Verlinde, W.G.Hol, E.Fan.

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.

Selected figure(s)

Figure 1.
Figure 1. Previously Studied Monovalent Ligands to CT and LT and Chemical Structure of Newly Synthesized Bivalent Ligands BV1–BV4

Figure 5.
Figure 5. Electron Density and Fitted Model(A) Electron density and model for BV1 in complex with CTB[5]. Electron density is contoured at 2σ in a σ[A]-weighted (mFo–DFc) difference map.(B) Electron density and model for BV4 in complex with CTB[5]. Electron density is contoured at 3σ in a σ[A]-weighted (mFo-DFc) difference map.

The above figures are reprinted by permission from Cell Press: Chem Biol (2004, 11, 1205-1215) copyright 2004.

Figures were selected by the author.