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Molecular Pharmacology

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Research ArticleArticle
Open Access

Direct Binding of the Corrector VX-809 to Human CFTR NBD1: Evidence of an Allosteric Coupling between the Binding Site and the NBD1:CL4 Interface

Rhea P. Hudson, Jennifer E. Dawson, P. Andrew Chong, Zhengrong Yang, Linda Millen, Philip J. Thomas, Christie G. Brouillette and Julie D. Forman-Kay
Molecular Pharmacology August 2017, 92 (2) 124-135; DOI: https://doi.org/10.1124/mol.117.108373
Rhea P. Hudson
Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada (R.P.H, J.E.D., P.A.C., J.D.F.-K.); Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada (J.D.F.-K.); Center for Structural Biology (Z.Y., C.G.B.) and Department of Chemistry (C.G.B.), University of Alabama at Birmingham, Birmingham, Alabama; and Department of Physiology, UT Southwestern Medical Center, Dallas, Texas (L.M., P.J.T.).
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Jennifer E. Dawson
Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada (R.P.H, J.E.D., P.A.C., J.D.F.-K.); Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada (J.D.F.-K.); Center for Structural Biology (Z.Y., C.G.B.) and Department of Chemistry (C.G.B.), University of Alabama at Birmingham, Birmingham, Alabama; and Department of Physiology, UT Southwestern Medical Center, Dallas, Texas (L.M., P.J.T.).
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P. Andrew Chong
Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada (R.P.H, J.E.D., P.A.C., J.D.F.-K.); Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada (J.D.F.-K.); Center for Structural Biology (Z.Y., C.G.B.) and Department of Chemistry (C.G.B.), University of Alabama at Birmingham, Birmingham, Alabama; and Department of Physiology, UT Southwestern Medical Center, Dallas, Texas (L.M., P.J.T.).
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Zhengrong Yang
Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada (R.P.H, J.E.D., P.A.C., J.D.F.-K.); Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada (J.D.F.-K.); Center for Structural Biology (Z.Y., C.G.B.) and Department of Chemistry (C.G.B.), University of Alabama at Birmingham, Birmingham, Alabama; and Department of Physiology, UT Southwestern Medical Center, Dallas, Texas (L.M., P.J.T.).
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Linda Millen
Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada (R.P.H, J.E.D., P.A.C., J.D.F.-K.); Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada (J.D.F.-K.); Center for Structural Biology (Z.Y., C.G.B.) and Department of Chemistry (C.G.B.), University of Alabama at Birmingham, Birmingham, Alabama; and Department of Physiology, UT Southwestern Medical Center, Dallas, Texas (L.M., P.J.T.).
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Philip J. Thomas
Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada (R.P.H, J.E.D., P.A.C., J.D.F.-K.); Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada (J.D.F.-K.); Center for Structural Biology (Z.Y., C.G.B.) and Department of Chemistry (C.G.B.), University of Alabama at Birmingham, Birmingham, Alabama; and Department of Physiology, UT Southwestern Medical Center, Dallas, Texas (L.M., P.J.T.).
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Christie G. Brouillette
Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada (R.P.H, J.E.D., P.A.C., J.D.F.-K.); Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada (J.D.F.-K.); Center for Structural Biology (Z.Y., C.G.B.) and Department of Chemistry (C.G.B.), University of Alabama at Birmingham, Birmingham, Alabama; and Department of Physiology, UT Southwestern Medical Center, Dallas, Texas (L.M., P.J.T.).
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Julie D. Forman-Kay
Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada (R.P.H, J.E.D., P.A.C., J.D.F.-K.); Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada (J.D.F.-K.); Center for Structural Biology (Z.Y., C.G.B.) and Department of Chemistry (C.G.B.), University of Alabama at Birmingham, Birmingham, Alabama; and Department of Physiology, UT Southwestern Medical Center, Dallas, Texas (L.M., P.J.T.).
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Article Information

vol. 92 no. 2 124-135
DOI 
https://doi.org/10.1124/mol.117.108373
PubMed 
28546419

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0026-895X
Online ISSN 
1521-0111
History 
  • Received January 17, 2017
  • Accepted May 17, 2017
  • Published online July 6, 2017.

Article Versions

  • Earlier version (May 25, 2017 - 13:15).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2017 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license.

Author Information

  1. Rhea P. Hudson,
  2. Jennifer E. Dawson,
  3. P. Andrew Chong,
  4. Zhengrong Yang,
  5. Linda Millen,
  6. Philip J. Thomas,
  7. Christie G. Brouillette, and
  8. Julie D. Forman-Kay
  1. Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada (R.P.H, J.E.D., P.A.C., J.D.F.-K.); Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada (J.D.F.-K.); Center for Structural Biology (Z.Y., C.G.B.) and Department of Chemistry (C.G.B.), University of Alabama at Birmingham, Birmingham, Alabama; and Department of Physiology, UT Southwestern Medical Center, Dallas, Texas (L.M., P.J.T.).
  1. Address correspondence to:
    Julie D. Forman-Kay, Room 20.9713, Molecular Medicine, Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada. E-mail: forman{at}sickkids.ca
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Molecular Pharmacology: 92 (2)
Molecular Pharmacology
Vol. 92, Issue 2
1 Aug 2017
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Research ArticleArticle

Direct Binding of the Corrector VX-809 to Human CFTR NBD1

Rhea P. Hudson, Jennifer E. Dawson, P. Andrew Chong, Zhengrong Yang, Linda Millen, Philip J. Thomas, Christie G. Brouillette and Julie D. Forman-Kay
Molecular Pharmacology August 1, 2017, 92 (2) 124-135; DOI: https://doi.org/10.1124/mol.117.108373

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Research ArticleArticle

Direct Binding of the Corrector VX-809 to Human CFTR NBD1

Rhea P. Hudson, Jennifer E. Dawson, P. Andrew Chong, Zhengrong Yang, Linda Millen, Philip J. Thomas, Christie G. Brouillette and Julie D. Forman-Kay
Molecular Pharmacology August 1, 2017, 92 (2) 124-135; DOI: https://doi.org/10.1124/mol.117.108373
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