Abstract
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.
Keywords: Alpha-methylacyl-CoA racemase, binding free energy calculations, homo sapiens, homology modelling, molecular docking, molecular dynamics, prostate cancer.
Current Cancer Drug Targets
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:
Keywords: Alpha-methylacyl-CoA racemase, binding free energy calculations, homo sapiens, homology modelling, molecular docking, molecular dynamics, prostate cancer.
Abstract: 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.
Export Options
About this article
Cite this article as:
Abbasi Wajid Sumra and Azam Sikander Syed, 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
DOI https://dx.doi.org/10.2174/156800961509151110145430 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Therapeutical Approaches of Vasoactive Intestinal Peptide as a Pleiotropic Immunomodulator
Current Pharmaceutical Design Nanotechnology Applications for Diffuse Intrinsic Pontine Glioma
Current Neuropharmacology Interaction of Biologically Active Amines with Mitochondria and Their Role in the Mitochondrial-Mediated Pathway of Apoptosis
Current Medicinal Chemistry Hormone Replacement Therapy in Rheumatoid Arthritis
Current Rheumatology Reviews Meet the Editorial Board:
Current Drug Targets Synthesis and Anti-tumor Activities of Novel Phenyl Substituted Suberoylanilide Hydroxamic Acid Derivatives Against Human Cancer Cells
Medicinal Chemistry Patent Selections:
Recent Patents on Anti-Cancer Drug Discovery Natural Compounds as Antagonists of Canonical Wnt/β-Catenin Signaling
Current Chemical Biology Medicinal Chemistry Approaches of Controlling Gastrointestinal Side Effects of Non-Steroidal Anti-Inflammatory Drugs. Endogenous Protective Mechanisms and Drug Design
Medicinal Chemistry Raf Inhibitors as Therapeutic Agents Against Neurodegenerative Diseases
CNS & Neurological Disorders - Drug Targets How and Why to Screen for CYP2D6 Interindividual Variability in Patients Under Pharmacological Treatments
Current Drug Metabolism Comparison of the Inhibitory Effects of Clotrimazole and Ketoconazole against Human Carboxylesterase 2
Current Drug Metabolism Cyclic Peptides that Govern Signal Transduction Pathways: From Prokaryotes to Multi-Cellular Organisms
Current Topics in Medicinal Chemistry Genome-Wide Integrated Analyses of Androgen Receptor Signaling in Prostate Cancer Based on High-Throughput Technology
Current Drug Targets The Utility of Chemotherapy in the Treatment of Metastatic Prostate Cancer
Anti-Cancer Agents in Medicinal Chemistry Genomic and Epigenetic Complexity of the FOXF1 Locus in 16q24.1: Implications for Development and Disease
Current Genomics Aptamers Against Cell Surface Receptors: Selection, Modification and Application
Current Medicinal Chemistry Identification of KEY lncRNAs and mRNAs Associated with Oral Squamous Cell Carcinoma Progression
Current Bioinformatics NBN Polymorphysms and Cancer Susceptibility: A Systematic Review
Current Genomics Editorial [Hot topic: (Part I) Recent Trends in Anti-Cancer Drug Discovery (Guest Editor: Fazlul H. Sarkar)]
Mini-Reviews in Medicinal Chemistry