1JQY

HEAT-LABILE ENTEROTOXIN B-PENTAMER WITH LIGAND BMSC-0010

Summary for 1JQY

• Entry DOI: 10.2210/pdb1jqy/pdb
• Related: 1FD7 1JR0 1LT6 1LTA 1LTS
• Descriptor: HEAT-LABILE ENTEROTOXIN B CHAIN, (3-NITRO-5-(3-MORPHOLIN-4-YL-PROPYLAMINOCARBONYL)PHENYL)-GALACTOPYRANOSIDE (3 entities in total)
• Functional Keywords: enterotoxin, receptor, ligand, b-pentamer, toxin
• Biological source: Escherichia coli
• Total number of polymer chains: 15
• Total formula weight: 183713.50

Authors

Merritt, E.A.,Hol, W.G.J. (deposition date: 2001-08-09, release date: 2002-05-08, Last modification date: 2024-10-16)

Primary citation

Pickens, J.C.,Merritt, E.A.,Ahn, M.,Verlinde, C.L.,Hol, W.G.,Fan, E.
Anchor-based design of improved cholera toxin and E. coli heat-labile enterotoxin receptor binding antagonists that display multiple binding modes.
Chem.Biol., 9:215-224, 2002

PubMed Abstract: The action of cholera toxin and E. coli heat-labile enterotoxin can be inhibited by blocking their binding to the cell-surface receptor GM1. We have used anchor-based design to create 15 receptor binding inhibitors that contain the previously characterized inhibitor MNPG as a substructure. In ELISA assays, all 15 compounds exhibited increased potency relative to MNPG. Binding affinities for two compounds, each containing a morpholine ring linked to MNPG via a hydrophobic tail, were characterized by pulsed ultrafiltration (PUF) and isothermal titration calorimetry (ITC). Crystal structures for these compounds bound to toxin B pentamer revealed a conserved binding mode for the MNPG moiety, with multiple binding modes adopted by the attached morpholine derivatives. The observed binding interactions can be exploited in the design of improved toxin binding inhibitors.

PubMed: 11880036
DOI: 10.1016/S1074-5521(02)00097-2

Experimental method

X-RAY DIFFRACTION (2.14 Å)