ArticleBiochemistry2012
Cross-linking mass spectrometry and mutagenesis confirm the functional importance of surface interactions between CYP3A4 and holo/apo cytochrome b(5).
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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
24 citing papers in PubMed, 38 citations in OpenAlex.
- The regulatory potential of cytochrome P450-adrenodoxin interactions: Insights toward understanding redox partner regulation in drug metabolizing enzymes.Drug metabolism and disposition: the biological fate of chemicals · 2026Review
- In silico screening and analysis of nonsynonymous SNPs in human CYP1A2 to assess possible associations with pathogenicity and cancer susceptibility.Scientific reports · 2021Article
- Evidence of Allosteric Coupling between Substrate Binding and Adx Recognition in the Vitamin D Carbon-24 Hydroxylase CYP24A1.Biochemistry · 2020Article
- Living with Oxygen.Accounts of chemical research · 2018Article
- Membrane-embedded substrate recognition by cytochrome P450 3A4.The Journal of biological chemistry · 2018Article
- Approaches and Recent Developments for the Commercial Production of Semi-synthetic Artemisinin.Frontiers in plant science · 2018Review
- Structural and functional effects of cytochromeThe Journal of biological chemistry · 2017Article
- Digging Deeper into CYP3A Testosterone Metabolism: Kinetic, Regioselectivity, and Stereoselectivity Differences between CYP3A4/5 and CYP3A7.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Facilitating identification of minimal protein binding domains by cross-linking mass spectrometry.Scientific reports · 2017Article
- Hepatic cytochromes P450: structural degrons and barcodes, posttranslational modifications and cellular adapters in the ERAD-endgame.Drug metabolism reviews · 2016Review
- The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function.Drug metabolism and disposition: the biological fate of chemicals · 2016Review
- Membrane Interactions, Ligand-Dependent Dynamics, and Stability of Cytochrome P4503A4 in Lipid Nanodiscs.Biochemistry · 2016Article
- Cytochrome P450 17A1 Interactions with the FMN Domain of Its Reductase as Characterized by NMR.The Journal of biological chemistry · 2016Article
- Human liver cytochrome P450 3A4 ubiquitination: molecular recognition by UBC7-gp78 autocrine motility factor receptor and UbcH5a-CHIP-Hsc70-Hsp40 E2-E3 ubiquitin ligase complexes.The Journal of biological chemistry · 2015Article
- Effect of Cytochrome b5 Content on the Activity of Polymorphic CYP1A2, 2B6, and 2E1 in Human Liver Microsomes.PloS one · 2015Article
- Catalytically relevant electrostatic interactions of cytochrome P450c17 (CYP17A1) and cytochrome b5.The Journal of biological chemistry · 2014Article
- Chemical cross-linking/mass spectrometry targeting acidic residues in proteins and protein complexes.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Enhanced identification of zero-length chemical cross-links using label-free quantitation and high-resolution fragment ion spectra.Journal of proteome research · 2014Article
- Hepatic cytochrome P450 ubiquitination: conformational phosphodegrons for E2/E3 recognition?IUBMB life · 2014Review
- Correlating structure and function of drug-metabolizing enzymes: progress and ongoing challenges.Drug metabolism and disposition: the biological fate of chemicals · 2014Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Cytochrome b(5) (cyt b(5)) is one of the key components in the microsomal cytochrome P450 monooxygenase system. Consensus has not been reached about the underlying mechanism of cyt b(5) modulation of CYP catalysis. Both cyt b(5) and apo b(5) are reported to stimulate the activity of several P450 isoforms. In this study, the surface interactions of both holo and apo b(5) with CYP3A4 were investigated and compared for the first time. Chemical cross-linking coupled with mass spectrometric analysis was used to identify the potential electrostatic interactions between the protein surfaces. Subsequently, the models of interaction of holo/apo b(5) with CYP3A4 were built using the identified interacting sites as constraints. Both cyt b(5) and apo b(5) were predicted to bind to the same groove on CYP3A4 with close contacts to the B-B' loop of CYP3A4, a substrate recognition site. Mutagenesis studies further confirmed that the interacting sites on CYP3A4 (Lys96, Lys127, and Lys421) are functionally important. Mutation of these residues reduced or abolished cyt b(5) binding affinity. The critical role of Arg446 on CYP3A4 in binding to cyt b(5) and/or cytochrome P450 reductase was also discovered. The results indicated that electrostatic interactions on the interface of the two proteins are functionally important. The results indicate that apo b(5) can dock with CYP3A4 in a manner analogous to that of holo b(5), so electron transfer from cyt b(5) is not required for its effects.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.