ArticleJournal of the American Chemical Society2011
Defining CYP3A4 structural responses to substrate binding. Raman spectroscopic studies of a nanodisc-incorporated mammalian cytochrome P450.
Article in Journal of the American Chemical Society, 2011. 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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Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- Mechanistic and spectroscopic characterization of human CYP17A1 in Nanodiscs.Journal of inorganic biochemistry · 2026Review
- Nanodisc-embedded cytochrome P450 P3A4 binds diverse ligands by distributing conformational dynamics to its flexible elements.Journal of inorganic biochemistry · 2023Article
- Revealing substrate-induced structural changes in active site of human CYP51 in the presence of its physiological substrates.Journal of inorganic biochemistry · 2023Article
- Label-free chemical imaging of cytochrome P450 activity by Raman microscopy.Communications biology · 2022Article
- Structure-function characterization of the mono- and diheme forms of MhuD, a noncanonical heme oxygenase from Mycobacterium tuberculosis.The Journal of biological chemistry · 2022Article
- Mechanism of Phellodendron and Anemarrhena Drug Pair on the Treatment of Liver Cancer Based on Network Pharmacology and Bioinformatics.Frontiers in oncology · 2022Article
- Probing Heme Active Sites of Hemoglobin in Functional Red Blood Cells Using Resonance Raman Spectroscopy.The journal of physical chemistry. B · 2021Article
- Nanodiscs: A toolkit for membrane protein science.Protein science : a publication of the Protein Society · 2021Review
- Expression, purification, and functional reconstitution ofBiochimica et biophysica acta. Biomembranes · 2020Article
- Correction to "Allosteric Interactions in Human Cytochrome P450 CYP3A4: The Role of Phenylalanine 213".Biochemistry · 2019Article
- Allosteric Interactions in Human Cytochrome P450 CYP3A4: The Role of Phenylalanine 213.Biochemistry · 2019Article
- Membrane-embedded substrate recognition by cytochrome P450 3A4.The Journal of biological chemistry · 2018Article
- Spectroscopic studies of the cytochrome P450 reaction mechanisms.Biochimica et biophysica acta. Proteins and proteomics · 2018Review
- Nanodiscs in Membrane Biochemistry and Biophysics.Chemical reviews · 2017Review
- Purification of family B G protein-coupled receptors using nanodiscs: Application to human glucagon-like peptide-1 receptor.PloS one · 2017Article
- Anisotropic metal growth on phospholipid nanodiscs via lipid bilayer expansion.Scientific reports · 2016Article
- The use of isomeric testosterone dimers to explore allosteric effects in substrate binding to cytochrome P450 CYP3A4.Journal of inorganic biochemistry · 2016Article
- Current Approaches for Investigating and Predicting Cytochrome P450 3A4-Ligand Interactions.Advances in experimental medicine and biology · 2015Review
- Resonance Raman spectroscopy reveals that substrate structure selectively impacts the heme-bound diatomic ligands of CYP17.Biochemistry · 2014Article
- Using resonance Raman cross-section data to estimate the spin state populations of Cytochromes P450.Journal of Raman spectroscopy : JRS · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Resonance Raman (RR) spectroscopy is used to help define active site structural responses of nanodisc-incorporated CYP3A4 to the binding of three substrates: bromocriptine (BC), erythromycin (ERY), and testosterone (TST). We demonstrate that nanodisc-incorporated assemblies reveal much more well-defined active site RR spectroscopic responses as compared to those normally obtained with the conventional, detergent-stabilized, sampling strategies. While ERY and BC are known to bind to CYP3A4 with a 1:1 stoichiometry, only the BC induces a substantial conversion from low- to high-spin state, as clearly manifested in the RR spectra acquired herein. The third substrate, TST, displays significant homotropic interactions within CYP3A4, the active site binding up to 3 molecules of this substrate, with the functional properties varying in response to binding of individual substrate molecules. While such behavior seemingly suggests the possibility that each substrate binding event induces functionally important heme structural changes, up to this time spectroscopic evidence for such structural changes has not been available. The current RR spectroscopic studies show clearly that accommodation of different size substrates, and different loading of TST, do not significantly affect the structure of the substrate-bound ferric heme. However, it is here demonstrated that the nature and number of bound substrates do have an extraordinary influence on the conformation of bound exogenous ligands, such as CO or dioxygen and its reduced forms, implying an effective mechanism whereby substrate structure can impact reactivity of intermediates so as to influence function, as reflected in the diverse reactivity of this drug metabolizing cytochrome.
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