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
Impact of brain tissue binding and plasma protein binding of drugs in DMPK
The impression of brain tissue binding (BTB) or plasma protein binding (PPB) in Drug Metabolism and Pharmacokinetics is critical to understanding the distribution, efficacy, and potential toxicity of drugs that target the central nervous system (CNS). BTB and high PPB influence the distribution of drugs in the body and their ...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
Safety evaluation of vaccine combination
Vaccine combination safety evaluation is a critical field within immunology and public health that focuses on assessing the safety and efficacy of combining different vaccines to maximize protection against various diseases while minimizing potential adverse effects. This process is significant because it ensures that vaccines can be administered together without ...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
-
UPLC-ESI-Q-TOF/MS Based Metabolic Profiling of Protosappanin B in Rat Plasma, Bile, Feces, Urine and Intestinal Bacteria Samples
Current Drug Metabolism Mitochondria-Mediated Oxidative Stress: Old Target for New Drugs
Current Medicinal Chemistry Antibacterial Drug Discovery in the Post-Genomics Era
Current Drug Targets - Infectious Disorders Structure-based Discovery of Narirutin as a Shikimate kinase Inhibitor with Anti-tubercular Potency
Current Computer-Aided Drug Design Penicillium marneffei and its Pulmonary Involvements
Current Respiratory Medicine Reviews Subject Index To Volume 8
Current Pharmaceutical Design An Overview of Neolignans of the Genus Piper L.: Isolation Methods and Biological Activities
Mini-Reviews in Medicinal Chemistry Antibody - Fc Receptor Interactions in Antimicrobial Functions
Current Immunology Reviews (Discontinued) Mycobacterium w Immunotherapy for Treating Pulmonary Tuberculosis - a Systematic Review
Current Pharmaceutical Design How to Make a Non-Antigenic Protein (Auto) Antigenic: Molecular Complementarity Alters Antigen Processing and Activates Adaptive-Innate Immunity Synergy
Anti-Cancer Agents in Medicinal Chemistry Microwave and Conventional Method Assisted Synthesis of 2-(substituted) -3-(4-methoxybenzyl) Thiazolidin-4-ones Using ZrOCl2·8H2O as a Catalyst
Current Microwave Chemistry Early Decision: Effector and Effector Memory T Cell Differentiation in Chronic Infection
Current Immunology Reviews (Discontinued) Marine Sponges: Potential Sources of New Antimicrobial Drugs
Current Pharmaceutical Biotechnology Formation of Mycobacterial Pellicles In Vitro and their Possible Impact on Tuberculosis Infection
Current Respiratory Medicine Reviews HtrA Protease Family as Therapeutic Targets
Current Pharmaceutical Design The Pivotal Role of Nitric Oxide: Effects on the Nervous and Immune Systems
Current Pharmaceutical Design Dried Blood Spots: A New Tool for Tuberculosis Treatment Optimization
Current Pharmaceutical Design Mycobacterial DNA Replication as a Target for Antituberculosis Drug Discovery
Current Topics in Medicinal Chemistry Recent Synthesis of Marine Natural Products with Antibacterial Activities
Anti-Infective Agents in Medicinal Chemistry Targeting HIV: Past, Present and Future
Infectious Disorders - Drug Targets