ArticleMolecular pharmacology2018
The X-Ray Crystal Structure of the Human Mono-Oxygenase Cytochrome P450 3A5-Ritonavir Complex Reveals Active Site Differences between P450s 3A4 and 3A5.
Article in Molecular pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Toxicity and DNA Adduct Formation Reinforce AI-Guided Prediction of Aflatoxin B1 Bioactivation in VERO E6 Cells.Toxins · 2026Article
- Ancestry informative genetic variants associated with tobacco metabolic and detoxification capacity measured by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) among smokers.Archives of toxicology · 2026Article
- Decoding the selective chemical modulation of CYP3A4.Nature communications · 2025Article
- Theoretical Study on the Metabolic Mechanism of Heptachlor in Human Cytochrome P450 Enzymes.International journal of molecular sciences · 2025Article
- In-silico screening and analysis of missense SNPs in human CYP3A4/5 affecting drug-enzyme interactions of FDA-approved COVID-19 antiviral drugs.Scientific reports · 2025Article
- Electron transfer in biological systems.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024Review
- Differential Effects of Clotrimazole on X-Ray Crystal Structures of Human Cytochromes P450 3A5 and 3A4.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Differences of Atomic-Level Interactions between Midazolam and Two CYP Isoforms 3A4 and 3A5.Molecules (Basel, Switzerland) · 2023Article
- Recombinant Technologies Facilitate Drug Metabolism, Pharmacokinetics, and General Biomedical Research.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- The inhibitory and inducing effects of ritonavir on hepatic and intestinal CYP3A and other drug-handling proteins.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- Epigenetic Mechanisms Contribute to Intraindividual Variations of Drug Metabolism Mediated by Cytochrome P450 Enzymes.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Human Cytochrome P450 1, 2, 3 Families as Pharmacogenes with Emphases on Their Antimalarial and Antituberculosis Drugs and Prevalent African Alleles.International journal of molecular sciences · 2023Review
- The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism?International journal of molecular sciences · 2022Review
- Identification of Potential Cytochrome P450 3A5 Inhibitors: An Extensive Virtual Screening through Molecular Docking, Negative Image-Based Screening, Machine Learning and Molecular Dynamics Simulation Studies.International journal of molecular sciences · 2022Article
- Interaction of CYP3A4 with Rationally Designed Ritonavir Analogues: Impact of Steric Constraints Imposed on the Heme-Ligating Group and the End-Pyridine Attachment.International journal of molecular sciences · 2022Article
- Elimination of tucatinib, a small molecule kinase inhibitor of HER2, is primarily governed by CYP2C8 enantioselective oxidation of gem-dimethyl.Cancer chemotherapy and pharmacology · 2022Article
- Structural characterization of the homotropic cooperative binding of azamulin to human cytochrome P450 3A5.The Journal of biological chemistry · 2022Article
- Unraveling the Structural Basis of Selective Inhibition of Human Cytochrome P450 3A5.Journal of the American Chemical Society · 2021Article
- Single Nucleotide Polymorphism Induces Divergent Dynamic Patterns in CYP3A5: A Microsecond Scale Biomolecular Simulation of Variants Identified in Sub-Saharan African Populations.International journal of molecular sciences · 2021Article
- Structural Basis for the Diminished Ligand Binding and Catalytic Ability of Human Fetal-Specific CYP3A7.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The contributions of cytochrome P450 3A5 to the metabolic clearance of marketed drugs is unclear, but its probable role is to augment the metabolism of several drugs that are largely cleared by P450 3A4. Selective metabolism by 3A4 is often a concern in drug development owing to potential drug-drug interactions and the variability of 3A4 and 3A5 expression. The contribution of P450 3A5 to these clearance pathways varies between individuals owing to genetic differences and similarities and differences in the metabolic properties of 3A5 compared with 3A4. To better understand the structural differences between P450s 3A4 and 3A5, the structure of 3A5 complexed with ritonavir was determined by X-ray crystallography to a limiting resolution of 2.91 Å. The secondary and tertiary structures of 3A5 and 3A4 are similar, but the architectures of their active sites differ. The 3A5 active site is taller and narrower than that of 3A4. As a result, ritonavir adopts a distinctly different conformation to fit into the cavity of 3A5 than seen for 3A4. These structural changes reflect amino acid differences that alter the conformation of the helix F through helix G region in the upper portion of the cavity and ionic interactions between residues in the beta-sheet domain that reduce the width of the cavity. The structural differences exhibited by 3A4 and 3A5 suggest that the overlap of catalytic activities may reflect molecular flexibility that determines how alternative conformers fit into the different active site architectures of the two enzymes.
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