Novel binding site identified in a hybrid between cholera toxin and heat-labile enterotoxin: 1.9 A crystal structure reveals the details.
Artikel i vetenskaplig tidskrift, 2004

A hybrid between the B subunits of cholera toxin and Escherichia coli heat-labile enterotoxin has been described, which exhibits a novel binding specificity to blood group A and B type 2 determinants. In the present investigation, we have determined the crystal structure of this protein hybrid, termed LCTBK, in complex with the blood group A pentasaccharide GalNAcalpha3(Fucalpha2)Galbeta4(Fucalpha3)GlcNAcbeta, confirming not only the novel binding specificity but also a distinct new oligosaccharide binding site. Binding studies revealed that the new specificity can be ascribed to a single mutation (S4N) introduced into the sequence of Escherichia coli heat-labile enterotoxin. At a resolution of 1.9 A, the new binding site is resolved in excellent detail. Main features include a complex network of water molecules, which is well preserved by the parent toxins, and an unexpectedly modest contribution to binding by the critical residue Asn4, which interacts with the ligand only via a single water molecule.

Protein Structure

genetics

Molecular

genetics

Water

chemistry

Glycosphingolipids

chemistry

metabolism

chemistry

Humans

Drug Design

metabolism

Models

Tertiary

genetics

metabolism

Binding Sites

Asparagine

Recombinant Fusion Proteins

metabolism

chemistry

Bacterial Toxins

metabolism

chemistry

Crystallography

metabolism

genetics

chemistry

Molecular Sequence Data

Blood Group Antigens

Escherichia coli Proteins

genetics

metabolism

genetics

chemistry

Cholera Toxin

Molecular Structure

metabolism

Protein Binding

Enterotoxins

metabolism

chemistry

Oligosaccharides

Protein Subunits

X-Ray

metabolism

chemistry

Författare

Åsa Holmner

Chalmers University of Technology

Michael Lebens

Göteborgs universitet

Susann Teneberg

Göteborgs universitet

Jonas Ångström

Göteborgs universitet

M. Ökvist

Göteborgs universitet

Ute Krengel

Chalmers, Institutionen för kemi och biovetenskap

Structure

0969-2126 (ISSN)

Vol. 12 1655-67

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1016/j.str.2004.06.022

PubMed

15341730