Modulation of ATP and drug binding by monoclonal antibodies against P-glycoprotein

E. Georges, Jian-Ting Zhang, V. Ling

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

The role of P-glycoprotein in mediating the drug-resistance phenotype in multidrug resistant cells is now well documented. It is thought to function as an energy-dependent drug-efflux pump of broad specificity. Structurally, P-glycoprotein is an internally duplicated molecule containing two large multi-spanning transmembrane domains and two cytoplasmic ATP binding domains. In this report we demonstrate that monoclonal antibodies C219, C494, and C32 directed against short linear regions of the P-glycoprotein molecule inhibit ATP binding to P-glycoprotein in vitro. We also provide direct evidence that both predicted ATP-binding domains bind ATP and that there is co-operativity between the two sites. In addition, the capacity of P-glycoprotein to bind the calcium channel blocker, azidopine, is inhibited differentially by the antibodies. These observations are the first evidence linking specific perturbations of the P-glycoprotein molecule with ATP and drug binding.

Original languageEnglish (US)
Pages (from-to)479-484
Number of pages6
JournalJournal of Cellular Physiology
Volume148
Issue number3
DOIs
StatePublished - 1991
Externally publishedYes

Fingerprint

P-Glycoprotein
Adenosine Triphosphate
Monoclonal Antibodies
Modulation
Pharmaceutical Preparations
Molecules
Calcium Channel Blockers
Drug Resistance
Pumps
Phenotype
Antibodies

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Modulation of ATP and drug binding by monoclonal antibodies against P-glycoprotein. / Georges, E.; Zhang, Jian-Ting; Ling, V.

In: Journal of Cellular Physiology, Vol. 148, No. 3, 1991, p. 479-484.

Research output: Contribution to journalArticle

Georges, E. ; Zhang, Jian-Ting ; Ling, V. / Modulation of ATP and drug binding by monoclonal antibodies against P-glycoprotein. In: Journal of Cellular Physiology. 1991 ; Vol. 148, No. 3. pp. 479-484.
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