Molecular modeling of the human multidrug resistance protein 1 (MRP1/ABCC1)
- Division of Cancer Biology and Genetics, Cancer Research Institute, Queen's University, Kingston, Ont., K7L 3N6 (Canada)
- Department of Biochemistry, Queen's University, Kingston, Ont., K7L 3N6 (Canada)
Multidrug resistance protein 1 (MRP1/ABCC1) is a 190 kDa member of the ATP-binding cassette (ABC) superfamily of transmembrane transporters that is clinically relevant for its ability to confer multidrug resistance by actively effluxing anticancer drugs. Knowledge of the atomic structure of MRP1 is needed to elucidate its transport mechanism, but only low resolution structural data are currently available. Consequently, comparative modeling has been used to generate models of human MRP1 based on the crystal structure of the ABC transporter Sav1866 from Staphylococcus aureus. In these Sav1866-based models, the arrangement of transmembrane helices differs strikingly from earlier models of MRP1 based on the structure of the bacterial lipid transporter MsbA, both with respect to packing of the twelve helices and their interactions with the nucleotide binding domains. The functional importance of Tyr{sup 324} in transmembrane helix 6 predicted to project into the substrate translocation pathway was investigated.
- OSTI ID:
- 21033037
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 365, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2007.10.141; PII: S0006-291X(07)02285-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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