Filgueira de Azevedo Walter, Gaspar Renato Tadeu, Canduri Fernanda, Camera João Carlos, Freitas da Silveira Nelson José
Departamento de Fi;sica, IBILCE, UNESP 15054-000, São José do Rio Preto, SP, Brazil.
Biochem Biophys Res Commun. 2002 Oct 11;297(5):1154-8. doi: 10.1016/s0006-291x(02)02352-5.
Here is described a structural model for the binary complex CDK5-roscovitine. Roscovitine has been shown to potently inhibit cyclin-dependent kinases 1, 2 and 5 (CDK1, 2, and 5), and the structure of CDK2 complexed with roscovitine has been reported; however, no structural data are available for complexes of CDK5 with inhibitors. The structural model indicates that roscovitine strongly binds to the ATP-binding pocket of CDK5 and structural comparison of the CDK2-roscovitine complex correlates the structural differences with differences in inhibition of these CDKs by this inhibitor. This structure opens the possibility of testing new inhibitor families, in addition to new substituents for the already known lead structures of adenine derivatives.
本文描述了CDK5-罗哌卡因二元复合物的结构模型。罗哌卡因已被证明能有效抑制细胞周期蛋白依赖性激酶1、2和5（CDK1、2和5），并且已经报道了与罗哌卡因复合的CDK2的结构；然而，关于CDK5与抑制剂复合物的结构数据尚无可用。该结构模型表明，罗哌卡因与CDK5的ATP结合口袋强烈结合，并且CDK2-罗哌卡因复合物的结构比较将结构差异与该抑制剂对这些CDK的抑制差异相关联。除了对腺嘌呤衍生物已知先导结构的新取代基之外，该结构为测试新的抑制剂家族开辟了可能性。
