Crystallographic analysis of an 8-mer p53 peptide analogue complexed with MDM2

被引：48

作者：

Sakurai, Kaori

Schubert, Carsten

Kahne, Daniel

机构：

[1] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA

[2] Johnson & Johnson Pharmaceut Res & Dev LLC, Exton, PA 19341 USA

[3] Harvard Univ, Sch Med, Dept Biol Cellular & Mol Pharmacol, Boston, MA 02115 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2006年 / 128卷 / 34期

关键词：

D O I：

10.1021/ja063102j

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The most potent inhibitor of the p53-MDM2 interaction reported to date is an 8-mer p53 peptide analogue (Novartis peptide), which contains 6-chlorotryptophane (Cl-Trp) and phosphonomethylphenylalanine (Pmp) as key residues for the enhanced activity. We report here a crystal structure of the co-complex between MDM2 and the Novartis peptide solved at 1.8 Å resolution. The structural basis for the role of the two aromatic residues are delineated by comparing the present structure with crystal structures of the MDM2 co-complex bound to other inhibitors including the wt-p53 peptide itself. Copyright © 2006 American Chemical Society.

引用

页码：11000 / 11001

页数：2

共 21 条

[11] SEVERAL HYDROPHOBIC AMINO-ACIDS IN THE P53 AMINO-TERMINAL DOMAIN ARE REQUIRED FOR TRANSCRIPTIONAL ACTIVATION, BINDING TO MDM-2 AND THE ADENOVIRUS-5 E1B 55-KD PROTEIN [J].