ArticleDrug metabolism and disposition: the biological fate of chemicals2010
CYP2C8 exists as a dimer in natural membranes.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Interplay of UDP-Glucuronosyltransferase and CYP2C8 for CYP2C8 Mediated Drug Oxidation and Its Impact on Drug-Drug Interaction Produced by Standardized CYP2C8 Inhibitors, Clopidogrel and Gemfibrozil.Clinical pharmacokinetics · 2024Article
- Functional characterization of CYP1 enzymes: Complex formation, membrane localization and function.Journal of inorganic biochemistry · 2023Article
- Inhibition of CYP2C8 by Acyl Glucuronides of Gemfibrozil and Clopidogrel: Pharmacological Significance, Progress and Challenges.Biomolecules · 2022Review
- Identification of the contact region responsible for the formation of the homomeric CYP1A2•CYP1A2 complex.The Biochemical journal · 2021Article
- Heteromeric complex formation between human cytochrome P450 CYP1A1 and heme oxygenase-1.The Biochemical journal · 2021Article
- Domain-Swap Dimerization ofMolecular pharmacology · 2020Article
- The Biosynthesis of Enzymatically Oxidized Lipids.Frontiers in endocrinology · 2020Review
- Targeting Kinases inFrontiers in veterinary science · 2020Article
- Critical Differences between Enzyme Sources in Sensitivity to Detect Time-Dependent Inactivation of CYP2C8.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Effects of polymorphic variation on the thermostability of heterogenous populations of CYP3A4 and CYP2C9 enzymes in solution.Scientific reports · 2018Article
- Characterization of Interactions Among CYP1A2, CYP2B4, and NADPH-cytochrome P450 Reductase: Identification of Specific Protein Complexes.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Physical Studies of P450-P450 Interactions: Predicting Quaternary Structures of P450 Complexes in Membranes from Their X-ray Crystal Structures.Frontiers in pharmacology · 2017Review
- Immobilized Cytochrome P450 for Monitoring of P450-P450 Interactions and Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- CYP2R1 Mutations Impair Generation of 25-hydroxyvitamin D and Cause an Atypical Form of Vitamin D Deficiency.The Journal of clinical endocrinology and metabolism · 2015Article
- Interactions among cytochromes P450 in microsomal membranes: oligomerization of cytochromes P450 3A4, 3A5, and 2E1 and its functional consequences.The Journal of biological chemistry · 2015Article
- Cytochrome P450 system proteins reside in different regions of the endoplasmic reticulum.The Biochemical journal · 2014Article
- Correlating structure and function of drug-metabolizing enzymes: progress and ongoing challenges.Drug metabolism and disposition: the biological fate of chemicals · 2014Review
- Interactions between cytochromes P450 2B4 (CYP2B4) and 1A2 (CYP1A2) lead to alterations in toluene disposition and P450 uncoupling.Biochemistry · 2013Article
- Identifying cytochrome p450 functional networks and their allosteric regulatory elements.PloS one · 2013Article
- Protein-protein and protein-membrane associations in the lignin pathway.The Plant cell · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
CYP2C8 with a modified N-terminal sequence (2C8H) crystallizes as a dimer, but it is not known whether native CYP2C8 exists as a dimer in natural membranes. We have examined the organization of 2C8H and CYP2C8 expressed in bacterial membranes and mammalian endoplasmic reticulum membranes, respectively, by cysteine scanning and cross-linking or oxidation of sulfhydryl groups. In both forms of CYP2C8, cross-linked dimers were observed that were eliminated by mutation of Cys-24 in the linker region. Introduction of individual cysteines in the N-terminal 21-amino acid membrane-spanning signal anchor resulted in a pattern of cross-linking consistent with an α-helical structure for the signal anchor. In the linker region, cross-linking was observed for cysteine substituted at residues 22, 23, or 24, just before three Arg residues, indicating close apposition of the two linker sequences despite the neighboring positive charges. Introduction into the F-G loop region of cysteine pairs optimally located for cross-linking based on the crystal structure resulted in cross-linked dimers in the Cys-24 mutant. Deletion of the signal anchor sequence eliminated cross-linking mediated by Cys-24 or by cysteines introduced in the F-G loop regions, indicating that the signal anchor interaction is required for stable dimer formation. These results indicate that the signal anchor sequence and the F-G loop region form interfaces for CYP2C8 intermolecular interactions in natural membranes.
Indexed as
Identifiers
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.