Abstract
Over the past decade, site-directed mutagenesis has become an essential tool in the study of mammalian cytochrome P450 structure-function relationships. Residues affecting substrate specificity, cooperativity, membrane localization, and interactions with redox partners have been identified using a combination of amino-acid sequence alignments, homology modeling, chimeragenesis, and site-directed mutagenesis. As homology modeling and substrate docking technology continue to improve, the ability to predict more precise functions for specific residues will also advance, making it possible to utilize site-directed mutagenesis to test these predictions. Future studies will employ site-directed mutagenesis to learn more about cytochrome P450 substrate access channels, to define the role of residues that do not lie within substrate recognition sites, to engineer additional soluble forms of microsomal cytochromes P450 for x-ray crystallography, and to engineer more efficient enzymes for drug activation and / or bioremediation.
Keywords: Mammalian Cytochrome P450 Structure, Mutagenesis, Chimeragenesis, Aflatoxin B1, naphthoflavone, Dehydroepiandrosterone
Current Drug Metabolism
Title: Analysis of Mammalian Cytochrome P450 Structure and Function by Site-Directed Mutagenesis
Volume: 2 Issue: 2
Author(s): T. L. Domanski and J. R. Halpert
Affiliation:
Keywords: Mammalian Cytochrome P450 Structure, Mutagenesis, Chimeragenesis, Aflatoxin B1, naphthoflavone, Dehydroepiandrosterone
Abstract: Over the past decade, site-directed mutagenesis has become an essential tool in the study of mammalian cytochrome P450 structure-function relationships. Residues affecting substrate specificity, cooperativity, membrane localization, and interactions with redox partners have been identified using a combination of amino-acid sequence alignments, homology modeling, chimeragenesis, and site-directed mutagenesis. As homology modeling and substrate docking technology continue to improve, the ability to predict more precise functions for specific residues will also advance, making it possible to utilize site-directed mutagenesis to test these predictions. Future studies will employ site-directed mutagenesis to learn more about cytochrome P450 substrate access channels, to define the role of residues that do not lie within substrate recognition sites, to engineer additional soluble forms of microsomal cytochromes P450 for x-ray crystallography, and to engineer more efficient enzymes for drug activation and / or bioremediation.
Export Options
About this article
Cite this article as:
Domanski L. T. and Halpert R. J., Analysis of Mammalian Cytochrome P450 Structure and Function by Site-Directed Mutagenesis, Current Drug Metabolism 2001; 2 (2) . https://dx.doi.org/10.2174/1389200013338612
DOI https://dx.doi.org/10.2174/1389200013338612 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
Call for Papers in Thematic Issues
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
Metabolism-Mediated Xenobiotic Toxicity
Considering the potent modulation of biotransformation enzyme expression and activities by various therapeutic drugs and environmental chemicals, and the commonly combined exposure of humans to both drugs and the ever increasing environmental pollutants simultaneously, knowledge about the combined toxic effects by modulating biotransformation enzymes, such as P450s, UDP- glucuronosyltransferases, and ...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

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Clinical Applications of Mesenchymal Stem Cells in Laryngotracheal Reconstruction
Current Stem Cell Research & Therapy Anti-seizure Effects and Mechanisms of Berberine: A Systematic Review
Current Pharmaceutical Biotechnology Seeing the Person in the Patient: Making the Case for Individualized PROMs in Mental Health Care
Current Psychiatry Reviews Estrogen: Roles in Spermatogenesis
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Regulatory T Cell Counts and Development of Malignancy in Patients with HIV Infection
Current HIV Research COX Inhibition and NSAID-Induced Gastric Damage - Roles in Various Pathogenic Events
Current Topics in Medicinal Chemistry Advances in Anticancer Antibody-Drug Conjugates and Immunotoxins
Recent Patents on Anti-Cancer Drug Discovery The beneficial effect of Cape gooseberry juice on carbon tetrachloride-induced neuronal damage
CNS & Neurological Disorders - Drug Targets Heme Oxygenase-1/Carbon Monoxide: Novel Therapeutic Strategies in Critical Care Medicine
Current Drug Targets Prospects for the Therapeutic Application of Lentivirus-Based Gene Therapy to HIV-1 Infection
Current Gene Therapy A Novel Method for the Syntheses of Imidazo-Thiadiazoles as Potential Antioxidants and Anti-Inflammatory Agents
Recent Advances in Inflammation & Allergy Drug Discovery Revealing Potential Binding Affinity of FDA Approved Therapeutics Targeting Main Protease (3CLpro) in Impairing Novel Coronavirus (SARSCoV- 2) Replication that Causes COVID-19
Coronaviruses Potential Prognostic Predictors and Molecular Targets for Skin Melanoma Screened by Weighted Gene Co-expression Network Analysis
Current Gene Therapy NF-κB in Systemic Lupus Erythematosus and Antiphospholipid Syndrome
Current Rheumatology Reviews The Complex Dynamics of Breast Cancer
Current Women`s Health Reviews Inflammatory Pathways in Knee Osteoarthritis: Potential Targets for Treatment
Current Rheumatology Reviews The Roles of Corticotropin Releasing Factor (CRF) in Responses to Emotional Stress: Is CRF Release a Cause or Result of Fear/Anxiety?
CNS & Neurological Disorders - Drug Targets Newer Approaches to the Discovery of Glitazones
Mini-Reviews in Organic Chemistry Viral Reservoirs an Impediment to HAART: New Strategies to Eliminate HIV-1
Current Drug Targets - Infectious Disorders Future Opportunities in Malaria Management Offered by Probiotics
Infectious Disorders - Drug Targets