Attachment of a ‘molecular spring’ restores drug-stimulated ATPase activity to P-glycoprotein lacking both Q loop glutamines

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• 作者：Tip W. Loo ; David M. Clarke ; ^{david.clarke@utoronto.ca}
• 关键词：P-glycoprotein ; ABC protein ; Disulfide cross-linking ; Molecular spring ; Drug-stimulated ATPase activity
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2017
• 出版时间：29 January 2017
• 年：2017
• 卷：483
• 期：1
• 页码：366-370
• 全文大小：654 K
• 卷排序：483

文摘

Mutation of Q-loop glutamines (Q475A/Q1118A) inhibited drug-stimulated ATPase activity in human P-glycoprotein. The Q475A/Q1118A mutations disrupted signaling between the transmembrane- and nucleotide-binding domains. Cross-linking of mutant L175C/N820C/Q475A/Q1118A with a flexible cross-linker restored drug-stimulated ATPase activity. Gln475 and Gln1118 form part of a spring-like mechanism required for open to closed conformational changes.