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学科主题: 物理化学
题名: Protonated Form: The Potent Form of Potassium-Competitive Acid Blockers
作者: Luo, Hua-Jun1;  Deng, Wei-Qiao1, 2;  Zou, Kun1
通讯作者: KunZou
刊名: PLOS ONE
发表日期: 2014-05-20
DOI: 10.1371/journal.pone.0097688
卷: 9, 期:5, 页:97688
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
英文摘要: Potassium-competitive acid blockers (P-CABs) are highly safe and active drugs targeting H+,K+-ATPase to cure acid-related gastric diseases. In this study, we for the first time investigate the interaction mechanism between the protonated form of P-CABs and human H+,K+-ATPase using homology modeling, molecular docking, molecular dynamics and binding free energy calculation methods. The results explain why P-CABs have higher activities with higher pKa values or at lower pH. With positive charge, the protonated forms of P-CABs have more competitive advantage to block potassium ion into luminal channel and to bind with H+,K+-ATPase via electrostatic interactions. The binding affinity of the protonated form is more favorable than that of the neutral P-CABs. In particular, Asp139 should be a very important binding site for the protonated form of P-CABs through hydrogen bonds and electrostatic interactions. These findings could promote the rational design of novel P-CABs.
关键词[WOS]: GASTROESOPHAGEAL-REFLUX DISEASE ;  GASTRIC H,K ATPASE ;  PUMP INHIBITORS ;  MONOFUMARATE TAK-438 ;  MUTATIONAL ANALYSIS ;  BINDING-SITES ;  DRUG TARGET ;  SCH 28080 ;  P-CAB ;  H+,K+-ATPASE
语种: 英语
WOS记录号: WOS:000339563400044
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/143984
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.China Three Gorges Univ, Coll Chem & Life Sci, Hubei Key Lab Nat Prod Res & Dev, Yichang, Hubei, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian, Liaoning, Peoples R China

Recommended Citation:
Luo, Hua-Jun,Deng, Wei-Qiao,Zou, Kun. Protonated Form: The Potent Form of Potassium-Competitive Acid Blockers[J]. PLOS ONE,2014,9(5):97688.
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