Determination and validation of mTOR kinase-domain 3D structure by homology modeling.
Determination and validation of mTOR kinase-domain 3D structure by homology modeling.
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DOI：
10.2147/ott.s84200
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发表时间：
2015
影响因子：
4
通讯作者：
Ibrahimi A
中科院分区：
文献类型：
--
作者：
Lakhlili W;Chevé G;Yasri A;Ibrahimi A
AKT/mammalian target of rapamycin（mTOR）通路被认为是人类癌症中常见的激活和失调的信号通路之一。mTOR与两种分子复合物中的其他蛋白质相关：mTOR复合物1/Raptor和mTOR复合物2/Rictor。利用相关的脂质激酶PI 3 K γ的晶体结构，我们建立了mTOR催化区的模型。通过同源建模程序SWISS-MODEL进行mTOR的三维（3D）结构的建模。使用PROTECH和PROVE软件对所获得的模型进行质量和验证。通过Ramachandran图评估蛋白质的整体立体化学性质。还通过已知抑制剂的对接进行模型验证。在本文中，我们描述并验证了mTOR催化位点的3D模型。
The AKT/mammalian target of rapamycin (mTOR) pathway is considered as one of the commonly activated and deregulated signaling pathways in human cancer. mTOR is associated with other proteins in two molecular complexes: mTOR complex 1/Raptor and the mTOR complex 2/Rictor. Using the crystal structure of the related lipid kinase PI3Kγ, we built a model of the catalytic region of mTOR. The modeling of the three-dimensional (3D) structure of the mTOR was performed by homology modeling program SWISS-MODEL. The quality and validation of the obtained model were performed using PROCHECK and PROVE softwares. The overall stereochemical property of the protein was assessed by the Ramachandran plot. The model validation was also done by docking of known inhibitors. In this paper, we describe and validate a 3D model for the mTOR catalytic site.