CYP3A4

Structure of CYP3A4

CYP3A4 is a medium-sized protein with a molecular weight of approximately 57 kDa. Due to differences in amino acid sequences and post-translational modifications, the molecular weight may vary slightly between different species. CYP3A4 is a monomeric enzyme protein composed of 502 amino acid residues. Its overall structure consists of multiple α-helices and several β-sheets, forming a compact globular conformation. The human CYP3A4 protein contains 223 α-helices, 27 β-turns, 72 extended chains, and 180 random coils. The N-terminal region of CYP3A4 also includes a transmembrane helix that anchors it to the endoplasmic reticulum membrane, enabling it to function within the cell. The CYP3A4 crystal contains a phenylalanine cluster composed of seven phenylalanine residues, which is closely associated with the activity of CYP3A4. Near the active site of CYP3A4, multiple conserved amino acid residues play a key role in substrate binding and catalytic reactions. CYP3A4 possesses variable regions whose conformational changes enable it to adapt to binding with different substrates, thereby exhibiting broad substrate specificity.

Key structural features of CYP3A4:

• Monomeric enzyme structure
• Presence of a phenylalanine cluster
• Dynamic hydrophobic channel guides substrates into the active site
• Conserved amino acid residues for substrate binding and catalysis
• Flexible structural domain

Functions of CYP3A4

Cytochrome P450 3A4 (CYP3A4) is one of the major drug-metabolizing enzymes in the human body, responsible for the metabolism of approximately 50% of clinically used medications. It plays a crucial role in the metabolism of endogenous substances, the detoxification of exogenous substances, drug-drug interactions, and the maintenance of intracellular redox balance.

Applications of CYP3A4 and CYP3A4 Targets in Literature

1. Yang, Yuting, et al. "Metabolomics-based discovery of XHP as a CYP3A4 inhibitor against pancreatic cancer." Frontiers in Pharmacology 14 (2023): 1164827. https://doi.org/10.3389/fphar.2023.1164827

The article reveals that CYP3A4 is a critical target in pancreatic cancer (PC) and demonstrates that Xihuang Pills (XHP) effectively inhibit CYP3A4, suppressing tumor growth and enhancing apoptosis. The findings highlight XHP's potential as a CYP3A4-targeted therapy for PC, offering a novel approach to combat chemoresistance and improve treatment outcomes.

2. Zhai, Qinglian, et al. "Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity". Frontiers in Pharmacology, 13, 912618. https://doi.org/10.3389/fphar.2022.912618

This article highlights the critical role of CYP3A4 in drug metabolism, accounting for up to 60% of clinically used drugs, and emphasizes the significant genetic variability (e.g., CYP3A4*22) contributing to interindividual differences in enzyme activity. The study underscores the need to explore rare genetic variants and regulatory mechanisms (e.g., nuclear receptors like PXR/CAR) to address the "missing heritability" in CYP3A4 pharmacogenomics. These insights could improve personalized drug dosing and clinical outcomes by better predicting CYP3A4-mediated metabolic variability.

3. Oladipo, Segun D., et al. "Ni²⁺ and Cu²⁺ complexes of N-(2,6-dichlorophenyl)-N-mesityl formamidine dithiocarbamate: structural and functional properties as CYP3A4 potential substrates." Scientific Reports 13 (2023): 13414. https://doi.org/10.1038/s41598-023-39502-x

This article presents a comprehensive structural- and simulation-based strategy to identify the nickel(II) and copper(II) dithiocarbamate complexes as high-affinity, substrate-mimicking ligands of CYP3A4, achieving predicted binding energies (−97 and −87 kcal mol⁻¹) that surpass those of classical inhibitors and the native heme substrate, offering a metal-centred route for fine-tuning CYP3A4 activity in drug-overexpression scenarios

4. Denisov, Ilia G., et al. "Midazolam as a probe for heterotropic drug-drug interactions mediated by CYP3A4." Biomolecules 12.6 (2022): 853. https://doi.org/10.3390/biom12060853

This article develops a nanodisc-based, midazolam-centered assay that exploits CYP3A4’s dual binding pockets to quantify allosteric drug–drug interactions, providing a reproducible, mechanistic and readily scalable platform for early prediction of metabolic liabilities in new drug candidates.

Creative Biolabs: CYP3A4 Target Research Solutions

Creative Biolabs specializes in the production of high-quality CYP3A4 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom CYP3A4 Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our CYP3A4 antibodies, custom preparations, or technical support, contact us at email.