Toxin project publications

TK Sixma, KH Kalk, BAM van Zanten, Z Dauter, J Kingma, B Witholt, & WGJ Hol (1993): Refined structure of Escherichia coli heat-labile enterotoxin, a close relative of cholera toxin. J Molec Biol 230, 890-918.

Publications 1994

EA Merritt, S Sarfaty, F van den Akker, C L'hoir, JA Martial, & WGJ Hol (1994a): Crystal structure of cholera toxin B-pentamer bound to receptor GM1 pentasaccharide. Protein Sci 3, 166-175.
EA Merritt, TK Sixma, KH Kalk, BAM van Zanten, & WGJ Hol (1994b): Galactose binding site in E. coli heat-labile enterotoxin (LT) and cholera toxin (CT). Molec Microbiol 13, 745-753.
EA Merritt, Pronk, SE, TK Sixma, KH Kalk, BAM van Zanten, & WGJ Hol (1994c): Structure of partially-activated E. coli heat-labile enterotoxin (LT) at 2.6Å resolution. FEBS Lett 337, 88-92.
M Pizza, M Domenighini, W Hol, V Giannelli, MR Fontana, MM Giuliani, C Magagnoli, S Peppoloni, R Manetti, & R Rappuoli (1994d): Probing the structure-activity relationship of Escherichia coli LT-A by site-directed mutagenesis. Molec Microbiol 14, 51-60.

Publications 1995

WGJ Hol, TK Sixma, & EA Merritt (1995a): Structure and function of E. coli heat labile enterotoxin and cholera toxin B-pentamer. In Bacterial Toxins and Virulence Factors in Disease, edited by Moss, Vaughan, Iglewski, & Tu. New York: M. Dekker.
EA Merritt, S Sarfaty, M Pizza, S Domenighini, R Rappuoli, & WGJ Hol(1995b): Mutation of a buried residue causes loss of activity but no conformational change in the heat-labile enterotoxin of Escherichia coli. Nature Structure Biology, 2, 269-272.
EA Merritt & WGJ Hol(1995c): AB₅ Bacterial Toxins. Current Opinion in Structural Biology 5, 165-171.
M Shoham, T Scherf, J Anglister, M Levitt, EA Merritt, & WGJ Hol (1995d): Structural Diversity in a Conserved Cholera Toxin Epitope Involved in Ganglioside Binding. Protein Science 4, 841-848.
EA Merritt, S Sarfaty, T Chang, LM Palmer, MG Jobling, RK Holmes, & WGJ Hol (1995e): Surprising leads for a cholera toxin receptor binding antagonist: Crystallographic studies of CTB mutants. Structure, 3: 561-570.
F van den Akker, EA Merritt, MG Pizza, M Domenighini, R Rappuoli, & WGJ Hol (1995f): The Arg7Lys mutant of heat-labile enterotoxin exhibits great flexibility of active site loop 47-56 of the A subunit. Biochemistry 34, 10996-11004.

Publications 1996

F van den Akker, E Steensma, & WGJ Hol (1996a). Tumor marker disaccharide D-Gal-ß1,3-GalNAc complexed to heat-labile enterotoxin from Escherichia coli. Protein Science 5, 1184-1188.
IK Feil, R Reddy, L de Haan, EA Merritt, F van den Akker, DR Storm, & WGJ Hol (1996b). Protein engineering studies of A chain loop 47 to 56 of Escherichia coli heat-labile enterotoxin point to a a prominent role of this loop for cytotoxicity. Molec Microbiol 20, 823-832.
F van den Akker, S Sarfaty, EM Twiddy, TD Connell, RK Holmes, & WGJ Hol (1996c). Crystal structure of a new heat-labile enterotoxin, LT-IIb Structure 4, 665-678.
EA Merritt, F van den Akker, & WGJ Hol (1996d). E.coli heat labile enterotoxin and cholera toxin B-pentamer - crystallographic studies of biological activity. In Protein Toxin Structure (ed: M.W. Parker) R.G. Landes 1996. Company, pp 147-172

Publications 1997

EA Merritt, S Sarfaty, MG Jobling, T-T Chang, RK Holmes, TR Hirst, & WGJ Hol (1997a). Structural studies of receptor binding by cholera toxin mutants. Protein Science 6, 1516-1528.
F van den Akker, IK Feil, C Roach, AA Platas, EA Merritt, & WGJ Hol (1997b). Crystal structure of a heat-labile enterotoxin from Escherichia coli with increased thermostability introduced by an engineered disulfide bond in the A subunit. Protein Science 6, 2644-2649
F van den Akker, M Pizza, R Rappuoli, & WGJ Hol (1997c). Crystal structure of a non-toxic mutant of heat-labile enterotoxin, which is a potent mucosal adjuvant. Protein Science 6, 2650-2654
EA Merritt, S Sarfaty, IK Feil, & WGJ Hol (1997d). Structural foundation for the design of receptor-binding antagonists targeting E. coli heat-labile enterotoxin. Structure 5, 1485-1499.

Publications 1998

L de Haan, WR Verweij, IK Feil, M Holtrop, WGJ Hol, E Agsteribbe, & J Wilschut (1998a). Role of GM1 binding in the mucosal immunogenicity and adjuvant activity of the Escherichia coli heat-labile enterotoxin and its B subunit. Immunology 94, 424-430.
L de Haan, IK Feil, WR Verweij, W Holtrop, WGJ Hol, E Agsteribbe, & J Wilschut (1998b). Mutational analysis of the role of ADP-ribosylation activity and GM1-binding activity in the adjuvant properties of the Escherichia coli heat-labile enterotoxin towards intranasally administered keyhole limpet hemocyanin. Eur. J. Immunol. 28, 1243-1250.
L de Haan, IK Feil, WR Verweij, W Holtrop, WGJ Hol, E Agsteribbe, & J Wilschut (1998c). Non-toxic variants of the Escherichia coli heat-labile enterotoxin as mucosal immunogens and adjuvants. S. T. P. Pharma Sciences 8, 75-80.A
EA Merritt, P Kuhn, S Sarfaty, JL Erbe, RK Holmes, & WGJ Hol (1998d). The 1.25Å resolution refinement of the cholera toxin B-pentamer: evidence of peptide backbone strain at the receptor-binding site. J Molec Biol 282, 1043-1059.
IK Feil, AA Platas, F van den Akker, R Reddy, EA Merritt, DR Storm, & WGJ Hol (1998e). Stepwise transplantation of an active site loop between heat-labile enterotoxins LT-II and LT-I and characterization of the obtained hybrid toxins. Protein Engineering 11, 1103-1109.

Publications 1999

BT Hovey, CLMJ Verlinde, EA Merritt, & WGJ Hol (1999a). Structure-based discovery of a pore-binding ligand: towards assembly inhibitors for cholera and related AB5 toxins. J Molec Biol 285, 1169-1178.
WE Minke, DJ Diller, WG Hol, & CL Verlinde (1999b). The role of waters in docking strategies with incremental flexibility for carbohydrate derivatives: heat-labile enterotoxin, a multivalent test case. J Med Chem 42, 1778-88.
WE Minke, C Roach, WG Hol, & CL Verlinde (1999c). Structure-based exploration of the ganglioside GM1 binding sites of Escherichia coli heat-labile enterotoxin and cholera toxin for the discovery of receptor antagonists. Biochemistry 38, 5684-92.
WE Minke, F Hong, CL Verlinde, WG Hol, & E Fan (1999d). Using a galactose library for exploration of a novel hydrophobic pocket in the receptor binding site of the Escherichia coli heat-labile enterotoxin. J Biol Chem 274, 33469-73.

Publications 2000

E Fan, Z Zhang, WE Minke, Z Hou, CLMJ Verlinde, & WGJ Hol (2000a). High-affinity pentavalent ligands of Escherichia coli heat-labile enterotoxin by modular structure-based design. J Am Chem Soc 122, 2663-2664.
E Fan, EA Merritt, CLMJ Verlinde, & WGJ Hol (2000b). AB₅ toxins: structures and inhibitor design. Current Opinion in Structural Biology 10, 680-686.
WE Minke, J Pickens, EA Merritt, E Fan, CLMJ Verlinde, & WGJ Hol (2000c). Structure of m-carboxyphenyl-- D-galactopyranoside complexed to heat-labile enterotoxin at 1.3 Å resolution: surprising variations in ligand-binding modes. Acta Cryst. D56, 795-804
F van den Akker, E Merritt, & WGJ Hol (2000d). Structure and function of cholera toxin and related enterotoxins. in Handbook of Experimental Pharmacology, Vol 145, pp 109-131. Springer-Verlag GmbH, Berlin, Germany.

Publications 2001

E Fan, EA Merritt, Z Zhang, JC Pickens, C Roach, M Ahn, & WGJ Hol (2001a). Exploration of the GM1 receptor-binding site of heat-labile enterotoxin and cholera toxin by phenyl-ring-containing galactose derivatives. Acta Cryst. D57, 201-212.
AT Aman, S Fraser, EA Merritt, C Rodigherio, M Kenny, M Ahn, WGJ Hol, NA Williams, WI Lencer, & TR Hirst (2001b). A mutant cholera toxin B subunit that binds GM1-ganglioside but lacks immunomodulatory or toxic activity. Proc. Natl. Acad. Sci. USA 98, 8536-8541.

Publications 2002

E Fan & EA Merritt (2002). Combating infectious diseases through multivalent design. Curr Drug Targets Infect Disord. 2, 161-167
JC Pickens, EA Merritt, M Ahn, CLMJ Verlinde, WGJ Hol, & E Fan (2002). Anchor-based design of improved cholera toxin and E coli heat-labile enterotoxin receptor binding antagonists that display multiple binding modes Chemistry & Biology 9, 215-224.
EA Merritt, Z Zhang, JC Pickens, M Ahn, WGJ Hol & E Fan (2002). Characterization and Crystal Structure of a High-Affinity Pentavalent Receptor-Binding Inhibitor for Cholera Toxin and E. coli Heat-Labile Enterotoxin J. Am. Chem. Soc. 124, 8818-8824.
Z Zhang, EA Merritt, M Ahn, C Roach, Z Hou, CLMJ Verlinde, WGJ Hol & E Fan (2002). Solution and crystallographic studies of branched multivalent ligands that inhibit the receptor-binding of cholera toxin J. Am. Chem. Soc. 124, 12991-12998.

Publications 2004

E Fan, CJ O'Neal, DD Mitchell, MA Robien, Z Zhang, JC Pickens, XJ Tan, K Korotkov, C Roach, B Krumm, CL Verlinde, EA Merritt, & WG Hol (2004). Structural biology and structure-based inhibitor design of cholera toxin and heat-labile enterotoxin Int J Med Microbiol. 294, 217-23.
Z Zhang, J Liu, CL Verlinde, WG Hol, & E Fan (2004). Large cyclic peptides as cores of multivalent ligands: application to inhibitors of receptor binding by cholera toxin. J Org Chem. 29, 7737-40.
JC Pickens, DD Mitchell, J Liu, X Tan, Z Zhang, CL Verlinde, WG Hol, & E Fan (2004). Nonspanning bivalent ligands as improved surface receptor binding inhibitors of the cholera toxin B pentamer. Chem Biol. 11, 1205-1215.
CJ O'Neal, EI Amaya, MG Jobling, RK Holmes, & WG Hol (2004). Crystal structures of an intrinsically active cholera toxin mutant yield insight into the toxin activation mechanism. Biochemistry 43, 3772-3782.
DD Mitchell, JC Pickens, K Korotkov, E Fan, & WG Hol (2004). 3,5-Substituted phenyl galactosides as leads in designing effective cholera toxin antagonists; synthesis and crystallographic studies. Bioorg Med Chem. 12, 907-920.

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