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
Exploring oxidative stress and the anti-oxidant defense system in chronic diseases: therapeutic strategies and future perspective
Ageing is facilitated by oxidative stress (OS), which happens spontaneously. Several studies have demonstrated that OS over an extended period of time has a role in the emergence of several chronic illnesses. Diabetes, cancer, and heart disease are a few examples of these ailments. An imbalance between the body's antioxidants ...read more
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
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
-
Targeting the Folate Receptor: Improving Efficacy in Inorganic Medicinal Chemistry
Current Medicinal Chemistry Combinatorial Approaches to Iminosugars as Glycosidase and Glycosyltransferase Inhibitors
Combinatorial Chemistry & High Throughput Screening Nanostructured Approaches for the Targeted Delivery of Antibiotics in Difficult Infections
Current Organic Chemistry State of the Art of Nanobiotechnology Applications in Neglected Diseases
Current Nanoscience An Efficient Gram Scale Synthesis of Aryl Iodides from Aryl Diazofluoroborates in Water under Mild Conditions
Letters in Organic Chemistry Drug Repurposing for the Treatment of Staphylococcal Infections
Current Pharmaceutical Design Nanoparticulate Drug Delivery System to Overcome the Limitations of Conventional Curcumin in the Treatment of Various Cancers: A Review
Drug Delivery Letters Meet Our Editorial Board Member:
Current Medicinal Chemistry Evaluation of the Combined Therapy of DA-7218, a New Oxazolidinone, and Trimethoprim/ Sulfamethoxazole in the Treatment of Experimental Actinomycetoma by Nocardia brasiliensis
Current Drug Delivery Perspectives and Prospects on mRNA Vaccine Development for COVID-19
Current Medicinal Chemistry Psoriatic Arthritis – Review of the Immunologic, Clinic and Therapeutic Aspects of an Inflammatory Systemic Disease
Current Rheumatology Reviews Design, Synthesis, Molecular Docking, and Anticancer Evaluation of Pyrazole Linked Pyrazoline Derivatives with Carbothioamide Tail as EGFR Kinase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry On the Design of Broad Based Screening Assays to Identify Potential Pharmacological Chaperones of Protein Misfolding Diseases
Current Topics in Medicinal Chemistry Management and Treatment of Dengue and Chikungunya - Natural Products to the Rescue
Combinatorial Chemistry & High Throughput Screening Privileged Structures in the Design of Potential Drug Candidates for Neglected Diseases
Current Medicinal Chemistry Dermatology and Global Health Meet Pharmacogenomics: Cutaneous Leishmaniasis
Current Pharmacogenomics and Personalized Medicine Drug Design and Identification of Potent Leads Against Mycobacterium tuberculosis Thymidine Monophosphate Kinase
Current Topics in Medicinal Chemistry Innovative Technologies for Oral Drug Delivery
Current Drug Delivery Bacterial Eukaryotic Type Serine-Threonine Protein Kinases: From Structural Biology to Targeted Anti-Infective Drug Design
Current Topics in Medicinal Chemistry The Release and Induced Immune Responses of a Plant-Made and Delivered Antigen in the Mouse Gut
Current Drug Delivery