Understanding the Impact of the P-loop Conformation on Kinase Selectivity

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• 作者：Cristiano R. W. Guimara虄es ; Brajesh K. Rai ; Michael J. Munchhof ; Shenping Liu ; Jian Wang ; Samit K. Bhattacharya ; Leonard Buckbinder
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2011
• 出版时间：June 27, 2011
• 年：2011
• 卷：51
• 期：6
• 页码：1199-1204
• 全文大小：853K
• 年卷期：v.51,no.6(June 27, 2011)
• ISSN：1549-960X

文摘

This work addresses the link between selectivity and an unusual, folded conformation for the P-loop observed initially for MAP4K4 and subsequently for other kinases. Statistical and computational analyses of our crystal structure database demonstrate that inhibitors that induce the P-loop folded conformation tend to be more selective, especially if they take advantage of this specific conformation by interacting more favorably with a conserved Tyr or Phe residue from the P-loop.