tailieunhanh - Báo cáo y học: " Binding site of ABC transporter homology models confirmed by ABCB1 crystal structure"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Binding site of ABC transporter homology models confirmed by ABCB1 crystal structure. | Theoretical Biology and Medical Modelling BioMed Central Research Binding site of ABC transporter homology models confirmed by ABCB1 crystal structure Aina W Ravna Ingebrigt Sylte and Georg Sager Open Access Address Department of Medical Pharmacology and Toxicology Institute of Medical Biology Faculty of Health Sciences University of Tromso N-9037 Tromso Norway Email Aina W Ravna - Ingebrigt Sylte - Georg Sager - Corresponding author Published 4 September 2009 Received 4 June 2009 Theoretical Biology and Medical Modelling 2009 6 20 doi 1742-4682-6-20 Accepted 4 September 2009 This article is available from http content 6 1 20 2009 Ravna et al licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract 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 site-directed mutagenesis studies. The ABCB1 ABCC4 and ABCC5 models display distinct differences in the electrostatic properties of their drug recognition .