Tumor suppressor p16INK4A:: Determination of solution structure and analyses of its interaction with cyclin-dependent kinase 4
Tumor suppressor p16INK4A:: Determination of solution structure and analyses of its interaction with cyclin-dependent kinase 4
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DOI：
10.1016/s1097-2765(00)80042-8
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发表时间：
1998-02-01
期刊：
影响因子：
16
通讯作者：
Tsai, MD
中科院分区：
文献类型：
--
作者：
Byeon, IJL;Li, JN;Tsai, MD
用核磁共振法测定了抑癌基因p16（INK 4A）的溶液结构，并确定了cdk 4和p16（INK 4A）的重要识别区。p16（INK 4A）的三级结构包含由三个环连接的四个螺旋-转角-螺旋基序。构建了12个p16（INK 4A）致瘤突变体，并对其结构和活性进行了分析，合理设计了新的突变体。cdk 4的N末端有一个58个残基的片段，对p16（INK 4A）的结合很重要。通过cdk 4的突变分析进一步验证了该区域的重要性。这些结果和对接实验已被用来评估p16（INK 4A）和cdk 4之间的可能的结合模式。
The solution structure of the tumor suppressor p16(INK4A) has been determined by NMR, and important recognition regions of both cdk4 and p16(INK4A) have been identified. The tertiary structure of p16(INK4A) contains four helix-turn-helix motifs linked by three loops. Twelve tumorigenic mutants of p16(INK4A) have been constructed and analyzed for their structure and activity, and new mutants have been designed rationally. A fragment of 58 residues at the N terminus of cdk4 important for p16(INK4A) binding has been identified. The importance of this region was further verified by mutational analysis of cdk4. These results and docking experiments have been used to assess possible modes of binding between p16(INK4A) and cdk4.