NMR characterization of kinase p38 dynamics in free and ligand-bound forms

被引：126

作者：

Vogtherr, M

Saxena, K

Hoelder, S

Grimme, S

Betz, M

Schieborr, U

Pescatore, B

Robin, M

Delarbre, L

Langer, T

Wendt, KU

Schwalbe, H

机构：

[1] Univ Frankfurt, Inst Organ Chem & Chem Biol, Ctr Biomol Magnet Resonance, D-60439 Frankfurt, Germany

[2] Sanofi Adventis Deutschland GmbH, D-65926 Frankfurt, Germany

[3] Sanofi Aventis, Ctr Rech Virty Seine, F-94403 Vitry Sur Seine, France

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2006年 / 45卷 / 06期

关键词：

drug design; enzyme inhibitors; NMR spectroscopy; protein kinases;

D O I：

10.1002/anie.200502770

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

(Figure Presented) In its apo state kinase p38 effects slow motions that can be detected in the NMR spectrum. One of the affected parts is the pharmacologically interesting DFG motif. Diarylurea inhibitors that bind to the DFG-out conformation lock this motif in a defined state, whereas DFG-in inhibitors that bind to the adjacent hinge region leave the flexibility of the DFG motif unaffected (see crystal structure of the complex of p38 with the inhibitor SB203580). © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：993 / 997

页数：5

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