【摘 要】
：
ATP-binding cassette(ABC)transporter multidrug resistance protein 4(MRP4,ABCC4)is involved in multidrug resistance(MDR),which is an increasing challenge to
【机 构】
：
State Key Laboratory of Natural and Biomimetic Drugs.School of Pharmaceutical Sciences,Peking Univer
【出 处】
：
第八届国际分子模拟与信息技术应用学术会议
论文部分内容阅读
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 cancers and infections.MRP4 is overexpressed in several types of cancers,and MRP4 inhibition shows striking effects against cancer progression and drug resistance.However,the structural knowledge of this protein remains unclear due to lack of an MRP4 X-ray structure,and homology modeling approach is an effective way to obtain three-dimensional structure of MRP4.We constructed three molecular models of human MRP4 mainly based on the inward facing Caenorhabditis elegans P-glyeoprotein(P-gp),the Thermotoga maritima heterodimeric ABC transporter TM287-TM288(TM287/288)and the outward facing Staphylococcus aureus Sav1866 crystal structures,which represented substrate uptake,transport and release state,respectively.The structures were further energy minimized and optimized by molecular dynamic simulations(MDS).All the models were validated by various tools and servers,and the results showed that the quality of the models was reasonable and acceptable.These MRP4 models could be used as working tools for experimental studies on the structure and functions of MRP4 and designing more specific membrane transport modulating agents(MTMA).
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