Novel binding site identified in a hybrid between cholera toxin and heat-labile enterotoxin: 1.9 A crystal structure reveals the details

Structure
Asa HolmnerUte Krengel

Abstract

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.

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Citations

Nov 16, 2012·Acta Crystallographica. Section D, Biological Crystallography·Vivian CodyGeorge Hajishengallis
Mar 10, 2009·Journal of Bacteriology·Benjamin MudrakMeta J Kuehn
Oct 15, 2010·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Debanu DasIan A Wilson
Jun 1, 2010·Toxins·Benjamin Mudrak, Meta J Kuehn
Aug 20, 2011·Carbohydrate Research·Pintu K Mandal, W Bruce Turnbull
Jun 26, 2007·Journal of Molecular Biology·Asa HolmnerUte Krengel
Feb 7, 2012·Biochemical and Biophysical Research Communications·Julie E HeggelundUte Krengel
May 11, 2016·The American Journal of Tropical Medicine and Hygiene·F Matthew KuhlmannJames M Fleckenstein
Apr 16, 2016·PLoS Pathogens·Julie Elisabeth HeggelundUte Krengel
Mar 3, 2019·Glycobiology·Hyun-Kyu ChoiHung-Jen Wu
May 10, 2019·Vox Sanguinis·Christopher P Stowell, Sean R Stowell
Dec 6, 2019·Organic & Biomolecular Chemistry·Diksha HaksarRoland J Pieters
Mar 10, 2018·Beilstein Journal of Organic Chemistry·Vajinder Kumar, W Bruce Turnbull
Feb 10, 2019·International Journal of Molecular Sciences·Julie Elisabeth HeggelundUte Krengel

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