Skip to main content
Home

Navigation controls

  • Search
  • Menu
September 9 – 12, 2025 | NIH Main Bethesda, Campus

Social

  • Twitter
  • Facebook
  • Email

Current Research Festival

  • 2025
  • 2024
    • General Schedule of Events
    • 2024 NIH Distinguished Scholars Program
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • National Academy of Science Mini-Symposium
    • Special Wednesday Events
    • Vendor Exhibit Information
    • Green Labs Fair
    • Research Festival Committee
  • 2023
    • General Schedule of Events
    • NIH Early–Career Investigator Lectures
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • Vendor Exhibit Information
    • Research Festival Committee
  • 2021
  • 2019
    • General Schedule of Events
    • Plenary Sessions
    • Poster Session
    • Data Blitz
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committee
  • 2018
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
  • 2017
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
  • 2016
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • Browse by Presenter Name
    • Browse by Presenter IC
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Tours of the National Library of Medicine and Clinical Center
    • Research Festival Committees
  • 2015
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Workshop Sessions
    • Poster Sessions
    • Browse by Presenter Name
    • Browse by Presenter IC
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • TSA Research Festival Exhibit Show
    • NIH Tours
    • Research Festival Committees
  • 2014
  • 2013
  • 2012
  • 2011
  • 2010
  • 2009
  • 2008
  • 2007
  • 2006
  • 2005
  • 2004
  • 2003
  • 2002
  • 2001
  • 2000

Main navigation

  • All Research Festivals
    • 2025
    • 2024
    • 2023
    • 2021
    • 2019
    • 2018
    • 2017
    • 2016
    • 2015
    • 2014
    • 2013
    • 2012
    • 2011
    • 2010
    • 2009
    • 2008
    • 2007
    • 2006
    • 2005
    • 2004
    • 2003
    • 2002
    • 2001
    • 2000

NIH Research Festival

September 16 – 18, 2015

Mechanism of the drug-mediated inhibition of P-glycoprotein ATPase activity: Role of hydrogen-bond interactions and structural motifs

Thursday, September 17, 2015 – Poster Session II
12:00 – 1:30 p.m.

FAES Terrace

NCI

CHEMBIO-2

Authors

  • EE Chufan
  • K Kapoor
  • SV Ambudkar

Abstract

P-glycoprotein (P-gp) is a member of the ATP-Binding Cassette transporter superfamily. This multidrug transporter utilizes energy from ATP hydrolysis for the efflux of a variety of hydrophobic and amphipathic compounds including anticancer drugs from the cell. Most of the substrates and modulators of P-gp stimulate its basal ATPase activity, although some inhibit it. The molecular mechanisms that are in play in either case are unknown. In this report, mutagenesis and molecular modeling studies on P-gp led to the identification of a pair of phenylalanine-tyrosine structural motifs in the transmembrane region that mediate the inhibition of ATP hydrolysis by certain drugs (zosuquidar, elacridar and tariquidar), with high affinity (IC50’s ranging from 10 to 30 nM). Upon mutation of any of these residues, drugs that inhibit the ATPase activity of P-gp switch to stimulation of the activity. Molecular modeling revealed that the phenylalanine residues F978 and F728 interact with tyrosine residues Y953 and Y310, respectively, in an edge-to-face conformation, which orients the tyrosines in such a way that they establish hydrogen-bond contacts with the inhibitor. Biochemical investigations along with transport studies in intact cells showed that the inhibitors bind at a high affinity site to produce inhibition of ATP hydrolysis and transport function. Upon mutation, they bind at lower affinity sites, stimulating ATP hydrolysis and only poorly inhibiting transport. These results also reveal that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for P-gp.

Scientific Focus Area: Chemical Biology

This page was last updated on Friday, March 26, 2021

  • General Schedule of Events
  • Plenary Sessions
  • Concurrent Workshop Sessions
  • Poster Sessions
  • Browse by Presenter Name
  • Browse by Presenter IC
  • FARE Award Ceremony
  • Future Research Leaders
  • Special Exhibits on Resources for Intramural Research
  • TSA Research Festival Exhibit Show
  • NIH Tours
  • Research Festival Committees

2015 program

Download the 2015 Research Festival Schedule Overview (6 pages)

  • Email
  • Print
  • Share Twitter Facebook LinkedIn

Current Research Festival

  • 2025
  • 2024
    • General Schedule of Events
    • 2024 NIH Distinguished Scholars Program
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • National Academy of Science Mini-Symposium
    • Special Wednesday Events
    • Vendor Exhibit Information
    • Green Labs Fair
    • Research Festival Committee
  • 2023
    • General Schedule of Events
    • NIH Early–Career Investigator Lectures
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • Vendor Exhibit Information
    • Research Festival Committee
  • 2021
  • 2019
    • General Schedule of Events
    • Plenary Sessions
    • Poster Session
    • Data Blitz
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committee
  • 2018
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
  • 2017
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
  • 2016
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • Browse by Presenter Name
    • Browse by Presenter IC
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Tours of the National Library of Medicine and Clinical Center
    • Research Festival Committees
  • 2015
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Workshop Sessions
    • Poster Sessions
    • Browse by Presenter Name
    • Browse by Presenter IC
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • TSA Research Festival Exhibit Show
    • NIH Tours
    • Research Festival Committees
  • 2014
  • 2013
  • 2012
  • 2011
  • 2010
  • 2009
  • 2008
  • 2007
  • 2006
  • 2005
  • 2004
  • 2003
  • 2002
  • 2001
  • 2000

Main navigation

  • All Research Festivals
    • 2025
    • 2024
    • 2023
    • 2021
    • 2019
    • 2018
    • 2017
    • 2016
    • 2015
    • 2014
    • 2013
    • 2012
    • 2011
    • 2010
    • 2009
    • 2008
    • 2007
    • 2006
    • 2005
    • 2004
    • 2003
    • 2002
    • 2001
    • 2000
  • Department of Health and Human Services
  • National Institutes of Health
  • USA.gov

Footer

  • Home
  • Contact Us
  • IRP
  • HHS Vulnerability Disclosure
  • Web Policies and Notices
  • Site Map
  • Search