Molecular modeling for the interaction between proteasome beta 5 subunit and organotin compounds

作     者：SHI GuoQing SUN Qing YANG HuanJie DOU QingPing DENG QianMin WANG HaiOu ZHONG GuangRong 

作者机构：Department of Biological Science and TechnologySchool of Applied ScienceUniversity of Science and Technology BeijingBeijing 100083China The Prevention ProgramBarbara Ann Karmanos Cancer Instituteand Departments of OncologyPathology and PharmacologySchool of MedicineWayne State UniversityDetroitMichiganMI 48201USA 

出 版 物：《Science China Chemistry》 (中国科学(化学英文版))

年 卷 期：2010年第53卷第11期

页      面：2387-2393页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (20977007) the Scientific Research Foundation for the Returned Overseas Chinese Scholars,Ministry of Education of China State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences (KF-2008-12) 

主　　题：docking organotin proteasome chymotrypsin-like activity 

摘      要：It has been reported that organotins can inhibit the proteasomal chymotrypsin-like activity and induce cell death,but the interaction mode of organotins with proteasome has not been well *** this study,the IC50 of butyltins and phenyltins against the proteasomal activity and the nature of their inhibition were *** was found that both mono-and di-organotins were weak,reversible inhibitors against the proteasome,while tributyltin and triphenyltin were potent,irreversible proteasome *** silico studies using the reversible organotin proteasome inhibitors demonstrated a tight correlation of the estimated proteasomal inhibition constants(Ki) with the experimental IC50 values for proteasome ***,the Sn atom in TBT and TPT was found susceptible to form a coordinate bond with Thr 1 OY of the β5 subunit,which may account for the irreversible proteasome *** computational docking approach well predicted the inhibition nature of organotins toward the proteasomal chymotrypsin-like *** predictive model might aid in understanding the cytotoxic behavior of similar organometallic compounds.