Molecular models of cyclin-dependent kinase 1 complexed with inhibitors
Molecular models of cyclin-dependent kinase 1 complexed with inhibitors
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DOI：
10.1016/j.bbrc.2004.09.109
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发表时间：
2004-11-12
影响因子：
3.1
通讯作者：
de Azevedo, WF
中科院分区：
文献类型：
--
作者：
Canduri, F;Uchoa, HB;de Azevedo, WF
Roscovitine和flavopiridol已被证明有效抑制细胞周期蛋白依赖性激酶1和2（CDK 1和2）。已经报道了CDK2与roscovitine和去氯匹罗啶醇复合的结构，但是没有晶体结构可用于CDK1与抑制剂的复合物。本工作描述了两个分子模型的二元复合物CDK1：roscovitine和CDK1：flavopiridol。这些结构模型表明，这两种抑制剂强烈结合到CDKI的ATP结合口袋和CDK复合物的结构比较相关的结构与这些CDK的抑制flavopiridol和roscovitine的差异。本文解释了这些抑制剂活性差异的结构基础。(C)2004爱思唯尔公司All rights reserved.
Roscovitine and flavopiridol have been shown to potently inhibit cyclin-dependent kinase 1 and 2 (CDK1 and 2). The structures of CDK2 complexed with roscovitine and deschoroflavopiridol have been reported, however no crystallographic structure is available for complexes of CDK1 with inhibitors. The present work describes two molecular models for the binary complexes CDK1:roscovitine and CDK1:flavopiridol. These structural models indicate that both inhibitors strongly bind to the ATP-binding pocket of CDKI and structural comparison of the CDK complexes correlates the structures with differences in inhibition of these CDKs by flavopiridol and roscovitine. This article explains the structural basis for the observed differences in activity of these inhibitors. (C) 2004 Elsevier Inc. All rights reserved.