Yamaguchi, Hideaki and Akitaya, Tatsuo and Kidachi, Yumi and Kamiie, Katsuyoshi and Umetsu, Hironori (2012) Homology modeling and structural analysis of human γ-glutamylcysteine ligase catalytic subunit for antitumor drug development. Journal of Biophysical Chemistry, 03 (03). pp. 238-248. ISSN 2153-036X
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Abstract
Homology modeling and structural analysis of human glutamate cysteine ligase catalytic subunit (hGCLC) were performed with a software package the Molecular Operating Environment. A yeast GCLC (yGCLC; PDB code: 3LVV) was selected as a template for the 3D structure modeling of hGCLC. The modeled hGCLC showed significant 3D similarities at the ligand biding site (LBS) to the yGCLC structure. The contact energy profiles of the hGCLC model were in good agreement with those of the yGCLC structure. Ramachandran plots revealed that only 1.4% of the amino acid residues were in the disfavored region for hGCLC. The molecular electrostatic potential (MEP) map of the hGCLC model exhibited that the model was slightly different from the yGCLC model electrostatically at the LBS. Further, docking simulations revealed the similarity of the ligand-receptor bound location between the hGCLC and yGCLC models. The different binding orientations between the glutathione (GSH)-hGCLC and GSH-yGCLC complexes reflected the different MEP maps at the LBSs between the hGCLC and yGCLC models. These results indicate that the hGCLC model was successfully modeled and analyzed. To the best of our knowledge, this is the first report of a hGCLC model with detailed analyses, and our data verify that the model can be utilized for application to target hGCLC for the development of anticancer drugs.
Item Type: | Article |
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Subjects: | Euro Archives > Chemical Science |
Depositing User: | Managing Editor |
Date Deposited: | 21 Apr 2023 04:34 |
Last Modified: | 01 Jul 2024 05:56 |
URI: | http://publish7promo.com/id/eprint/1002 |