α-甲基酰基辅酶A消旋酶的结构特征：比较结构建模，分子对接和动态模拟研究

Title:Structural Characterization of Alpha-methylacyl-CoA Racemase: Comparative Structural Modeling, Molecular Docking and Dynamic Simulations Studies

Volume: 15 Issue: 9

Author(s): Sumra Wajid Abbasi and Syed Sikander Azam

Affiliation:

关键词: α-甲基酰基辅酶A消旋酶，结合自由能计算，智人，同源建模，分子对接，分子动力学，前列腺癌

摘要: α-Methylacyl-CoA racemase (AMACR) has recently been reported as a vital solid tumor marker and is an attractive target for designing anti-tumor agents. It is a mitochondrial and peroxisomal enzyme which plays a central role in the oxidation of cholesterol metabolites and branched chain fatty acids. The three dimensional structure of human AMACR is still unknown. In the current study, homology model using Modeller and different modelling servers based on 1X74A as template is reported. The three dimensional model generated was validated and evaluated using various available programs like PROCHECK, ERRAT, ProSA energy plots, etc. In order to find potent inhibitors of AMACR, a docking study using compounds reported to be active against this enzyme of other organisms was conducted. Among the studied inhibitors, 2-methylmyristoyl- CoA effectively binds to and inhibits the enzyme by means of hydrogen bond interactions with the key residues of pocket. Moreover, molecular dynamics simulation was carried out to check the stability of AMACR/2-methylmyristoyl-CoA complex. The results illustrated the ligand’s high binding affinity with enzyme and the stability of hydrogen bond interactions in dynamic condition. Hence, 2-methylmyristoyl-CoA has been suggested to be a promising lead compound for the design of new inhibitors against AMACR.

Cite this article as:

Sumra Wajid Abbasi and Syed Sikander Azam , Structural Characterization of Alpha-methylacyl-CoA Racemase: Comparative Structural Modeling, Molecular Docking and Dynamic Simulations Studies, Current Cancer Drug Targets 2015; 15 (9) . https://dx.doi.org/10.2174/156800961509151110145430