Santhosh Sankar , Preeti Preeti , Kavya Ravikumar , Amrendra Kumar , Yedu Prasad , Sukriti Pal , Desirazu N. Rao , Handanahal S. Savithri , Nagasuma Chandra
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引用次数: 0
摘要
s -腺苷蛋氨酸(SAM)是一种普遍存在的辅助因子,作为甲基化反应的供体,并且在各种其他生化反应中还作为其他官能团(如氨基和核糖基)的供体。这种功能上的多功能性是由于SAM能够被多种不同序列和结构折叠的蛋白质分子识别。为了了解是什么导致了不同蛋白质中特定的SAM结合,我们开始研究它们的结合位点是否存在任何结构模式。通过全对比较和聚类对SAM结合位点的结构进行综合分析,发现存在4种不同的位点类型,其中只有一种得到了充分的研究。对于每种位点类型,我们破译了不同蛋白质识别SAM所涉及的共同最小原则,并推导出SAM结合特征的结构基序。在SAM位点中,氨基酸精确三维排列的结构基序的存在似乎是独立进化的,表明这些是赢得SAM识别的残基排列。此外,我们发现其中一种SAM位点类型与一种已知的ATP结合位点类型之间存在高度相似性。我们通过体外实验证明,已知的SAM结合蛋白HpyAII。M1是一种2型甲基转移酶,可以结合并水解ATP。我们发现了共同的结构基序,解释了这一点,进一步支持通过定点诱变。在具有不同序列和结构折叠的多个蛋白质家族中,观察到结合两种最普遍的配体的相似基序,在分子水平上为趋同进化提供了令人信服的证据。