Definition of the binding mode of a new class of phosphoinositide 3-kinase α-selective inhibitors using in vitro mutagenesis of non-conserved amino acids and kinetic analysis.
作者： Zhaohua Zheng , Syazwani I. Amran , Jiuxiang Zhu , Oleg Schmidt-Kittler , Kenneth W. Kinzler
DOI: 10.1042/BJ20120499
关键词:
摘要: The binding mechanism of a new class lipid-competitive, ATP non-competitive, p110α isoform-selective PI3K (phosphoinositide 3-kinase) inhibitors has been elucidated. Using the novel technique isoform reciprocal mutagenesis non-conserved amino acids in and p110β isoforms, we have identified three unique mechanisms for p110α-selective PIK-75, A-66S J-32. Each inhibitor’s p110α-isoform-selective was found to be due interactions with different within p110. PIK-75 interaction bound region 2 acid Ser 773 , 1 nonconserved Gln 859 J-32 had an indirect Lys 776 Ile 771 . is shown important analytical tool rational design inhibitors.
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