Abstract
The important role of high-resolution crystal structures of cytochrome P450 (CYP) enzymes for the generation of P450 models by homology is discussed. The main focus is on human P450 enzymes involved in drug metabolism, where the role of homology modelling has been emphasized in the recent literature. Report of the first human P450 crystal structure has provided an opportunity for comparison between those modelled from other crystallographic templates, and the recent substrate-bound rabbit CYP2C5 structure exemplifies the relevance of high-resolution template structures to generating 3-D models of P450s where the homology is relatively high. In particular, the homology models of human CYP1 and CYP2 family enzymes are presented, where good agreement with experiment findings are apparent.
Keywords: Cytochromes P450, Human Drug Metabolism, Structural Modeling
Current Drug Metabolism
Title: Investigating Human P450s Involved in Drug Metabolism via Homology with High-Resolution P450 Crystal Structures of the CYP2C Subfamily
Volume: 7 Issue: 6
Author(s): David F.V. Lewis, Yuko Ito and Peter S. Goldfarb
Affiliation:
Keywords: Cytochromes P450, Human Drug Metabolism, Structural Modeling
Abstract: The important role of high-resolution crystal structures of cytochrome P450 (CYP) enzymes for the generation of P450 models by homology is discussed. The main focus is on human P450 enzymes involved in drug metabolism, where the role of homology modelling has been emphasized in the recent literature. Report of the first human P450 crystal structure has provided an opportunity for comparison between those modelled from other crystallographic templates, and the recent substrate-bound rabbit CYP2C5 structure exemplifies the relevance of high-resolution template structures to generating 3-D models of P450s where the homology is relatively high. In particular, the homology models of human CYP1 and CYP2 family enzymes are presented, where good agreement with experiment findings are apparent.
Export Options
About this article
Cite this article as:
Lewis F.V. David, Ito Yuko and Goldfarb S. Peter, Investigating Human P450s Involved in Drug Metabolism via Homology with High-Resolution P450 Crystal Structures of the CYP2C Subfamily, Current Drug Metabolism 2006; 7 (6) . https://dx.doi.org/10.2174/138920006778017812
DOI https://dx.doi.org/10.2174/138920006778017812 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
Call for Papers in Thematic Issues
Interaction between drugs and endocrine diseases
The introduction of highly active antiretroviral therapy accelerated studies and our understanding on the interaction between pharmacological therapies and endocrine diseases. Drugs can precipitate endocrine via different mechanisms, including direct alteration of hormone production and secretion, dysregulation of hormonal axis, effects on hormonal transport, receptor-binding, and cellular signalling. Common drug-induced ...read more
Tissue Distribution and Metabolism of Micro- and Nanoparticles and Medical Implants
With the continuous advancement of modern science and engineering, numerous functional materials and active molecules have been developed and utilized in various industrial, medical, and food applications. Many of these can enter the body, either actively or passively, and have significant and intricate impacts on human health. For example, biomaterials ...read more
Related Journals
- 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
- Announcements
Related Articles
-
Synthesis and Antimycobacterial Evaluation of N-(E)-heteroaromaticpyrazine-2-carbohydrazide Derivatives
Medicinal Chemistry A Role of the 9-Aminoacridines and their Conjugates in a Life Science
Current Protein & Peptide Science Interleukin-6 In Rheumatoid Arthritis - From The Laboratory To The Bedside
Current Pharmaceutical Design Isothiouronium Salts Reduce NRAS Expression, Induce Apoptosis and Decrease Invasion of Melanoma Cells
Anti-Cancer Agents in Medicinal Chemistry Fracture Risk Associated with Use of Antibiotics
Current Drug Safety Exploring Promising Immunomodulatory Potential of Natural and Synthetic 1,3-Diphenyl-2-propen-1-one Analogs: A Review of Mechanistic Insight
Mini-Reviews in Medicinal Chemistry Biodegradable Polymeric Nanoparticles as the Delivery Carrier for Drug
Current Drug Delivery Leishmaniasis: History, Evolution of Treatment and the Need for New Drugs
Current Biotechnology Patent Selections:
Recent Patents on Anti-Infective Drug Discovery Interaction of Host Pattern Recognition Receptors (PRRs) with <i>Mycobacterium Tuberculosis</i> and Ayurvedic Management of Tuberculosis: A Systemic Approach
Infectious Disorders - Drug Targets Importance of a Potential Salt Bridge and Hydrophobic Core in the Function and Oligomerization of a Small Heat Shock Protein
Protein & Peptide Letters IP6 (Inositol Hexaphosphate) as a Signaling Molecule
Current Signal Transduction Therapy Benzothiazol Clubbed Imidazol-4-ones as Anti-fungal, Anti-tubercular and Anti-HIV-1 Agents: Their Synthesis and Molecular Docking Study
Letters in Drug Design & Discovery Recent Patents on Oral Vaccine Design
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Association between the Use of Inhaled Corticosteroids and Pulmonary Nontuberculous Mycobacterial Infection: A Systematic Review
Current Respiratory Medicine Reviews Selected Pharmaceutical Excipient Prevent Isoniazid and Rifampicin Induced Hepatotoxicity
Current Drug Metabolism Estrogen Receptor Beta (ERβ) Expression in Different Subtypes of Malignant Pleural Mesothelioma
Current Respiratory Medicine Reviews Micronutrients at the Interface Between Inflammation and Infection Ascorbic Acid and Calciferol. Part 1: General Overview with a Focus on Ascorbic Acid
Inflammation & Allergy - Drug Targets (Discontinued) Deep Transfer Learning for COVID-19 Prediction: Case Study for Limited Data Problems
Current Medical Imaging Impairment of T Cell Immunity by the Respiratory Syncytial Virus: Targeting Virulence Mechanisms for Therapy and Prophylaxis
Current Medicinal Chemistry