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Theoretical Biology and Medical Modelling

, 6:20

First Online: 04 September 2009Received: 04 June 2009Accepted: 04 September 2009DOI: 10.1186-1742-4682-6-20

Cite this article as: Ravna, A.W., Sylte, I. & Sager, G. Theor Biol Med Model 2009 6: 20. doi:10.1186-1742-4682-6-20


The human ATP-binding cassette ABC transporters ABCB1, ABCC4 and ABCC5 are involved in resistance to chemotherapeutic agents. Here we present molecular models of ABCB1, ABCC4 and ABCC5 by homology based on a wide open inward-facing conformation of Escherichia coli MsbA, which were constructed in order to elucidate differences in the electrostatic and molecular features of their drug recognition conformations. As a quality assurance of the methodology, the ABCB1 model was compared to an ABCB1 X-ray crystal structure, and with published cross-linking and site directed mutagenesis data of ABCB1. Amino acids Ile306 TMH5, Ile340 TMH6, Phe343 TMH6, Phe728 TMH7, and Val982 TMH12, form a putative substrate recognition site in the ABCB1 model, which is confirmed by both the ABCB1 X-ray crystal structure and the site-directed mutagenesis studies. The ABCB1, ABCC4 and ABCC5 models display distinct differences in the electrostatic properties of their drug recognition sites.

Electronic supplementary materialThe online version of this article doi:10.1186-1742-4682-6-20 contains supplementary material, which is available to authorized users.

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Autor: Aina W Ravna - Ingebrigt Sylte - Georg Sager


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