Tumor suppressor p16INK4A:: Determination of solution structure and analyses of its interaction with cyclin-dependent kinase 4

被引：131

作者：

Byeon, IJL

Li, JN

Ericson, K

Selby, TL

Tevelev, A

Kim, HJ

O'Maille, P

Tsai, MD

机构：

[1] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA

[2] Ohio State Univ, Dept Biochem, Columbus, OH 43210 USA

来源：

MOLECULAR CELL | 1998年 / 1卷 / 03期

关键词：

D O I：

10.1016/S1097-2765(00)80042-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：421 / 431

页数：11

共 55 条

[1] Cyclin-dependent kinase inhibitors (CKIs) and hematological malignancies [J].