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.

Water

metabolism

X-Ray

Asparagine

metabolism

genetics

chemistry

chemistry

Humans

Molecular Structure

genetics

Molecular

Escherichia coli Proteins

Enterotoxins

genetics

chemistry

Protein Structure

Crystallography

Drug Design

Blood Group Antigens

Bacterial Toxins

genetics

chemistry

chemistry

metabolism

metabolism

chemistry

metabolism

Recombinant Fusion Proteins

metabolism

Protein Binding

metabolism

Tertiary

genetics

genetics

metabolism

metabolism

Cholera Toxin

chemistry

Protein Subunits

Oligosaccharides

Models

Glycosphingolipids

Binding Sites

chemistry

chemistry

metabolism

Molecular Sequence Data

Författare

Åsa Holmner

Chalmers

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 9 1655-67

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1016/j.str.2004.06.022

PubMed

15341730

Mer information

Senast uppdaterat

2018-09-10