Binding site of ABC transporter homology models confirmed by ABCB1 crystal structure
Permanent lenke
https://hdl.handle.net/10037/2193Dato
2009-09-04Type
Journal articleTidsskriftartikkel
Peer reviewed
Sammendrag
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 crosslinking
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 sitedirected
mutagenesis studies. The ABCB1, ABCC4 and ABCC5 models display distinct differences
in the electrostatic properties of their drug recognition sites.
Forlag
BioMed CentralSitering
Theoretical Biology and Medical Modelling 2009, 6:20Metadata
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