Structural biology and structure-based inhibitor design of cholera toxin and heat-labile enterotoxin

Erkang Fan; Claire J. O'Neal; Daniel D. Mitchell; Mark A. Robien; Zhongsheng Zhang; Jason C. Pickens; Xiao Jian Tan; Konstantin Korotkov; Claudia Roach; Brian Krumm; Christophe L.M.J. Verlinde; Ethan A. Merritt; Wim G.J. Hol

doi:10.1016/j.ijmm.2004.07.002

Structural biology and structure-based inhibitor design of cholera toxin and heat-labile enterotoxin

Erkang Fan, Claire J. O'Neal, Daniel D. Mitchell, Mark A. Robien, Zhongsheng Zhang, Jason C. Pickens, Xiao Jian Tan, Konstantin Korotkov, Claudia Roach, Brian Krumm, Christophe L.M.J. Verlinde, Ethan A. Merritt, Wim G.J. Hol

Research output: Contribution to journal › Review article › peer-review

42 Scopus citations

Abstract

Structural biology studies on cholera toxin and the closely related heat-labile enterotoxin from enterotoxigenic Escherichia coli over the past decade have shed light on the mechanism of toxin action at molecular and atomic levels. Also, components of the extracellular protein secretion apparatus that translocate the toxins across the outer membrane are being investigated. At the same time, structure-based design has led to various classes of compounds targeting different toxin sites, including highly potent multivalent inhibitors that block the toxin receptor-binding process.

Original language	English
Pages (from-to)	217-223
Number of pages	7
Journal	International Journal of Medical Microbiology
Volume	294
Issue number	4
DOIs	https://doi.org/10.1016/j.ijmm.2004.07.002
State	Published - Oct 2004

Bibliographical note

Funding Information:
We thank the National Institutes of Health for financial support of our work (AI44954 to E. Fan; GM54618 to C. Verlinde; and AI34501 to W. Hol). C. O’Neal is a Howard Hughes Medical Institute predoctoral fellow. We are grateful to current and past members of our laboratories who have made contribution to the work described here, particularly in structural biology: Titia Sixma, Focco van den Akker, Ingeborg Feil, Bianca Nerenberg, Misol Ahn, Jan Abendroth, Steve Sarfaty, Stewart Turley, and Francis Athappilly; in inhibitor design: Wendy Sanderson; and in chemical synthesis: Zhen Hou, Feng Hong, Ajit Ghosh, Zhenfa Zhang and Jiyun Liu. We also like to thank our numerous collaborators including: Bernard Witholt, Rino Rappuoli, Joseph Martial, Randall Holmes, Michael Jobling, Timothy Hirst, Maria Sandkvist and Michael Bagdasarian.

Keywords

Cholera toxin
Heat-labile enterotoxin
Multivalent inhibitor
Structure-based drug design
Type II secretion system

ASJC Scopus subject areas

Microbiology
Microbiology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ijmm.2004.07.002

Cite this

Fan, E., O'Neal, C. J., Mitchell, D. D., Robien, M. A., Zhang, Z., Pickens, J. C., Tan, X. J., Korotkov, K., Roach, C., Krumm, B., Verlinde, C. L. M. J., Merritt, E. A., & Hol, W. G. J. (2004). Structural biology and structure-based inhibitor design of cholera toxin and heat-labile enterotoxin. International Journal of Medical Microbiology, 294(4), 217-223. https://doi.org/10.1016/j.ijmm.2004.07.002

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title = "Structural biology and structure-based inhibitor design of cholera toxin and heat-labile enterotoxin",

abstract = "Structural biology studies on cholera toxin and the closely related heat-labile enterotoxin from enterotoxigenic Escherichia coli over the past decade have shed light on the mechanism of toxin action at molecular and atomic levels. Also, components of the extracellular protein secretion apparatus that translocate the toxins across the outer membrane are being investigated. At the same time, structure-based design has led to various classes of compounds targeting different toxin sites, including highly potent multivalent inhibitors that block the toxin receptor-binding process.",

keywords = "Cholera toxin, Heat-labile enterotoxin, Multivalent inhibitor, Structure-based drug design, Type II secretion system",

author = "Erkang Fan and O'Neal, {Claire J.} and Mitchell, {Daniel D.} and Robien, {Mark A.} and Zhongsheng Zhang and Pickens, {Jason C.} and Tan, {Xiao Jian} and Konstantin Korotkov and Claudia Roach and Brian Krumm and Verlinde, {Christophe L.M.J.} and Merritt, {Ethan A.} and Hol, {Wim G.J.}",

note = "Funding Information: We thank the National Institutes of Health for financial support of our work (AI44954 to E. Fan; GM54618 to C. Verlinde; and AI34501 to W. Hol). C. O{\textquoteright}Neal is a Howard Hughes Medical Institute predoctoral fellow. We are grateful to current and past members of our laboratories who have made contribution to the work described here, particularly in structural biology: Titia Sixma, Focco van den Akker, Ingeborg Feil, Bianca Nerenberg, Misol Ahn, Jan Abendroth, Steve Sarfaty, Stewart Turley, and Francis Athappilly; in inhibitor design: Wendy Sanderson; and in chemical synthesis: Zhen Hou, Feng Hong, Ajit Ghosh, Zhenfa Zhang and Jiyun Liu. We also like to thank our numerous collaborators including: Bernard Witholt, Rino Rappuoli, Joseph Martial, Randall Holmes, Michael Jobling, Timothy Hirst, Maria Sandkvist and Michael Bagdasarian.",

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Fan, E, O'Neal, CJ, Mitchell, DD, Robien, MA, Zhang, Z, Pickens, JC, Tan, XJ, Korotkov, K, Roach, C, Krumm, B, Verlinde, CLMJ, Merritt, EA & Hol, WGJ 2004, 'Structural biology and structure-based inhibitor design of cholera toxin and heat-labile enterotoxin', International Journal of Medical Microbiology, vol. 294, no. 4, pp. 217-223. https://doi.org/10.1016/j.ijmm.2004.07.002

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T1 - Structural biology and structure-based inhibitor design of cholera toxin and heat-labile enterotoxin

AU - Fan, Erkang

AU - O'Neal, Claire J.

AU - Mitchell, Daniel D.

AU - Robien, Mark A.

AU - Zhang, Zhongsheng

AU - Pickens, Jason C.

AU - Tan, Xiao Jian

AU - Korotkov, Konstantin

AU - Roach, Claudia

AU - Krumm, Brian

AU - Verlinde, Christophe L.M.J.

AU - Merritt, Ethan A.

AU - Hol, Wim G.J.

N1 - Funding Information: We thank the National Institutes of Health for financial support of our work (AI44954 to E. Fan; GM54618 to C. Verlinde; and AI34501 to W. Hol). C. O’Neal is a Howard Hughes Medical Institute predoctoral fellow. We are grateful to current and past members of our laboratories who have made contribution to the work described here, particularly in structural biology: Titia Sixma, Focco van den Akker, Ingeborg Feil, Bianca Nerenberg, Misol Ahn, Jan Abendroth, Steve Sarfaty, Stewart Turley, and Francis Athappilly; in inhibitor design: Wendy Sanderson; and in chemical synthesis: Zhen Hou, Feng Hong, Ajit Ghosh, Zhenfa Zhang and Jiyun Liu. We also like to thank our numerous collaborators including: Bernard Witholt, Rino Rappuoli, Joseph Martial, Randall Holmes, Michael Jobling, Timothy Hirst, Maria Sandkvist and Michael Bagdasarian.

PY - 2004/10

Y1 - 2004/10

N2 - Structural biology studies on cholera toxin and the closely related heat-labile enterotoxin from enterotoxigenic Escherichia coli over the past decade have shed light on the mechanism of toxin action at molecular and atomic levels. Also, components of the extracellular protein secretion apparatus that translocate the toxins across the outer membrane are being investigated. At the same time, structure-based design has led to various classes of compounds targeting different toxin sites, including highly potent multivalent inhibitors that block the toxin receptor-binding process.

AB - Structural biology studies on cholera toxin and the closely related heat-labile enterotoxin from enterotoxigenic Escherichia coli over the past decade have shed light on the mechanism of toxin action at molecular and atomic levels. Also, components of the extracellular protein secretion apparatus that translocate the toxins across the outer membrane are being investigated. At the same time, structure-based design has led to various classes of compounds targeting different toxin sites, including highly potent multivalent inhibitors that block the toxin receptor-binding process.

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KW - Heat-labile enterotoxin

KW - Multivalent inhibitor

KW - Structure-based drug design

KW - Type II secretion system

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SN - 1438-4221

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Structural biology and structure-based inhibitor design of cholera toxin and heat-labile enterotoxin

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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