Molecular model of the outward facing state of the human multidrug resistance protein 4 (MRP4/ABCC4).
ATP-binding cassette (ABC) transporter multidrug resistance protein 4 (MRP4, ABCC4) is involved in multidrug resistance (MDR), which is an increasing challenge to the treatment of cancer and infections. We have constructed a molecular model of ABCC4 based on the outward facing Sav1866 crystal structure using molecular modeling techniques. Amino acids reported by ICMPocketFinder to take part in substrate translocation were among others Glu103 (TMH1), Ser328 (TMH5), Gly359 (TMH6), Arg362 (TMH6), Val726 (TMH7), and Leu987 (TMH12), and their corresponding amino acids in ABCB1 (P-glycoprotein) have been reported to be involved in drug binding according to site-directed mutagenesis studies. The ABCC4 model may be used as a working tool for experimental studies on ABCC4 and design of more specific membrane transport modulating agents (MTMA).
Department of Pharmacology, Institute of Medical Biology, University of Tromsø, N-9037 Tromsø, Norway. Aina.W.Ravna@fagmed.uit.no
Aina Westrheim
AW
Ravna
Georg
G
Sager
D000596:Amino Acids / Q000737:chemistry; D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D000596:Amino Acids; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C073492:ABCC4 protein, human