GO:0097243 flavonoid binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0097243 flavonoid binding is a molecular function defined as binding to a flavonoid, a compound containing two or more aromatic rings, each bearing at least one aromatic hydroxyl and connected with a carbon bridge.
• Flavonoid binding underlies diverse biological processes including rhizobial NodD activation by plant flavonoids, cold tolerance via CPK27-HY5 signaling in tomato, and transcriptional regulation of flavonoid biosynthesis by CtMYB1.
• Human serum albumin (HSA) is a major flavonoid-binding protein, and hydroxyl substitution patterns on flavonoids significantly affect HSA binding affinity [5,6].
• Flavonoid binding to GABA(A) receptors is associated with anxiolytic properties, while flavonoid-DNA binding has been characterized thermodynamically.
• Experimental approaches to study flavonoid binding include flavonoid probes, multispectral spectroscopy, molecular simulations, and CRISPR-based gene editing to dissect binding-protein function.
• EDITGENE provides knockout, point-mutation, knock-in, overexpression cell models and CRISPR library screening to study genes involved in flavonoid binding.
Description
Flavonoid binding (GO:0097243) is a molecular function that describes the selective interaction of a protein or other macromolecule with a flavonoid compound. Flavonoids are polyphenolic molecules characterized by two or more aromatic rings, each bearing at least one aromatic hydroxyl group, connected by a carbon bridge. This binding event is central to many biological processes, from symbiotic signaling in plants to modulation of human drug-metabolizing enzymes and receptors [1,5,7]. Understanding flavonoid binding is therefore relevant across plant biology, pharmacology, and nutrition. Recent studies have elucidated the molecular basis of flavonoid recognition by rhizobial NodD proteins, revealing how specific flavonoid structures activate transcriptional regulators. In tomato, CPK27 phosphorylates HY5 to promote flavonoid biosynthesis, indirectly linking flavonoid-binding events to cold tolerance. In safflower, CtMYB1 regulates flavonoid biosynthesis by binding to CAACCA elements, highlighting the interplay between flavonoid-binding transcription factors and biosynthetic gene expression. These examples underscore the importance of flavonoid binding in diverse physiological contexts. For researchers, flavonoid binding represents a tractable molecular function to study using biochemical, structural, and genetic approaches. The development of flavonoid probes has enabled direct characterization of binding modes with target proteins such as quercetin derivatives. Human serum albumin (HSA) is a well-studied flavonoid-binding protein, and its interactions with flavonoids are influenced by hydroxyl substitution patterns, as shown by multispectral spectroscopy and molecular simulations [5,6]. Flavonoid binding to GABA(A) receptors has been linked to anxiolytic properties, and flavonoid-DNA binding has been characterized thermodynamically. These findings illustrate the broad relevance of flavonoid binding across biological systems.
flavonoid binding At A Glance
| GO ID | GO:0097243 |
|---|---|
| GO term | flavonoid binding |
| Ontology | molecular_function |
| Synonym | none |
| Major function | Binding to flavonoids, polyphenolic compounds with two or more aromatic rings bearing hydroxyl groups |
| Definition source | QuickGO |
| Related processes | Rhizobial NodD activation, cold tolerance, flavonoid biosynthesis regulation |
| Example binding proteins | NodD, HY5, CtMYB1, human serum albumin [5,6], GABA(A) receptor |
What Is GO:0097243?
Flavonoid binding (GO:0097243) is defined as the binding to a flavonoid, a compound containing two or more aromatic rings, each bearing at least one aromatic hydroxyl and connected with a carbon bridge. This molecular function encompasses non-covalent interactions between a binding partner (typically a protein) and a flavonoid ligand. The definition emphasizes the structural features of flavonoids: multiple aromatic rings with hydroxyl groups and a carbon bridge. This function is distinct from flavonoid biosynthesis or metabolism; it specifically refers to the binding event itself.
Why Is flavonoid binding Important in Cell Biology?
Flavonoid binding is important because it mediates critical biological interactions across kingdoms, from symbiotic signaling between rhizobia and legumes to regulation of flavonoid biosynthesis in plants [2,3] and modulation of human drug targets and transport proteins [5,6,7]. Dysregulation of flavonoid binding can impact plant stress responses, nutritional quality, and human health. Moreover, flavonoid binding is a key mechanism for the biological activity of dietary flavonoids, influencing their pharmacokinetics and pharmacodynamics [5,6].
• Mediates rhizobial NodD activation by plant flavonoids, essential for symbiotic nitrogen fixation.
• Contributes to cold tolerance in tomato via CPK27-HY5 signaling and flavonoid biosynthesis.
• Regulates flavonoid biosynthesis through transcription factors like CtMYB1 that bind DNA elements.
• Determines the bioavailability and distribution of flavonoids in humans via binding to serum albumin [5,6].
• Underlies anxiolytic effects through flavonoid binding to GABA(A) receptors.
• Involved in flavonoid-DNA interactions with potential implications for gene regulation and genotoxicity.
• Provides targets for developing flavonoid-based probes and therapeutics.
• Enables CRISPR-based functional studies of genes encoding flavonoid-binding proteins.
Molecular Mechanism of flavonoid binding
Flavonoid recognition and binding site architecture
In simple terms: Proteins have specific pockets that recognize the shape and chemical groups of flavonoids.
Flavonoid-binding proteins typically possess aromatic and polar residues that form stacking and hydrogen-bonding interactions with the flavonoid's aromatic rings and hydroxyl groups. The molecular basis of flavonoid binding to rhizobial NodD involves specific recognition of flavonoid structures that activate the protein. Hydroxyl substitution patterns on flavonoids significantly affect binding to human serum albumin, as shown by multispectral spectroscopy and molecular simulations. Flavonoid probes have been developed to characterize the binding mode of quercetin derivatives with target proteins.
Thermodynamics and kinetics of flavonoid binding
In simple terms: Binding strength and speed depend on the flavonoid and protein involved.
Flavonoid-DNA binding studies have provided thermodynamic parameters, revealing the driving forces behind these interactions. Flavonoid binding to human serum albumin has been characterized biochemically. The binding affinity can vary with flavonoid structure, as demonstrated for hydroxyl substitution patterns.
Cofactors and regulation of flavonoid binding
In simple terms: Other molecules and modifications can influence how well flavonoids bind.
Phosphorylation of HY5 by CPK27 promotes flavonoid biosynthesis, indirectly affecting flavonoid-binding events in tomato. CtMYB1 regulates flavonoid biosynthesis by binding to CAACCA elements, linking DNA binding to flavonoid production. The binding of flavonoids to GABA(A) receptors is associated with anxiolytic properties, indicating receptor-level modulation.
Biological outcomes of flavonoid binding
In simple terms: When flavonoids bind, they can turn processes on or off.
Flavonoid binding to NodD activates rhizobial symbiotic genes. In tomato, flavonoid biosynthesis promoted by CPK27-HY5 enhances cold tolerance. Flavonoid binding to GABA(A) receptors produces anxiolytic effects. Flavonoid-DNA binding may have implications for gene expression.
Key Genes Involved in GO:0097243 flavonoid binding
The following genes and proteins are involved in flavonoid binding or related processes, as supported by the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| NodD | Rhizobial transcriptional activator that binds flavonoids | Molecular basis of flavonoid binding and activation |
| CPK27 | Calcium-dependent protein kinase that phosphorylates HY5 | Enhances cold tolerance via flavonoid biosynthesis |
| HY5 | Transcription factor phosphorylated by CPK27 | Promotes flavonoid biosynthesis |
| CtMYB1 | MYB transcription factor binding CAACCA elements | Regulates flavonoid biosynthesis in safflower |
| HSA | Human serum albumin, major plasma protein | Flavonoid binding affects pharmacokinetics [5,6] |
| GABA(A) receptor | Ligand-gated ion channel | Flavonoid binding with anxiolytic property |
| Quercetin derivatives | Flavonoid probes | Binding mode characterization |
| DNA | Genetic material | Flavonoid-DNA binding thermodynamics |
How Is flavonoid binding Regulated?
Flavonoid binding can be regulated at multiple levels. In tomato, CPK27 phosphorylates HY5 to promote flavonoid biosynthesis, indirectly influencing flavonoid-binding events. CtMYB1 regulates flavonoid biosynthesis by binding to CAACCA elements, linking transcriptional control to flavonoid availability. The binding of flavonoids to human serum albumin is modulated by hydroxyl substitution patterns, affecting affinity and specificity. Additionally, flavonoid binding to GABA(A) receptors is associated with anxiolytic effects, suggesting receptor-level regulation.
flavonoid binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| GABA(A) receptor | Anxiety disorders | Knockout or point-mutation cell models to study flavonoid binding |
| HSA | Drug pharmacokinetics | Overexpression or knockout of HSA in hepatic cell lines |
| CPK27 | Cold stress tolerance | Knockout tomato or cell lines to assess flavonoid binding |
| CtMYB1 | Flavonoid biosynthesis regulation | Knockout or overexpression in safflower cell cultures |
| NodD | Symbiotic nitrogen fixation | Knockout rhizobial strains to study flavonoid activation |
Flavonoid binding in neurological disorders
Flavonoid binding to GABA(A) receptors has been linked to anxiolytic properties, suggesting potential relevance for anxiety disorders. This interaction modulates receptor activity, which could influence neuronal excitability and behavior.
Flavonoid binding and cancer
While direct evidence for flavonoid binding in cancer is limited in the provided citations, flavonoids are known to interact with various cellular targets. Human serum albumin binding affects flavonoid bioavailability, which may impact cancer chemoprevention [5,6]. Further research is needed to establish causal links.
Flavonoid binding in plant stress responses
In tomato, flavonoid biosynthesis promoted by CPK27-HY5 enhances cold tolerance, indicating a role for flavonoid-binding events in stress adaptation. In safflower, CtMYB1 regulates flavonoid biosynthesis, which may affect plant defense and development.
From flavonoid binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does knockout of a candidate flavonoid-binding protein alter flavonoid response? | CRISPR knockout cell line |
| Does a specific point mutation in the binding pocket affect flavonoid affinity? | Point-mutation knock-in cell line |
| Can a tagged version of the protein be used to pull down flavonoids? | Tagged knock-in cell line |
| Does overexpression of the binding protein enhance flavonoid sensitivity? | Overexpression cell line |
| Which genes are essential for flavonoid binding in a genome-wide screen? | CRISPR library screening |
| What is the transcriptional response to flavonoid binding? | RNA-seq after flavonoid treatment |
How to Study the flavonoid binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Fluorescence spectroscopy | Binding affinity and thermodynamic parameters | Flavonoid-HSA binding [5,6] |
| Molecular simulations | Binding mode and interactions | Flavonoid-HSA binding |
| Flavonoid probes | Binding mode of quercetin derivatives | Target protein characterization |
| Isothermal titration calorimetry | Thermodynamics of flavonoid-DNA binding | DNA-flavonoid interactions |
| CRISPR knockout | Loss-of-function effects on flavonoid binding | Gene function studies |
| RNA-seq | Transcriptional changes | Flavonoid response pathways |
| CRISPR library screening | Genome-wide identification of regulators | Novel flavonoid-binding genes |
| Receptor binding assays | Flavonoid-GABA(A) receptor interaction | Anxiolytic drug discovery |
Biochemical binding assays
Flavonoid probes have been developed to characterize the binding mode of quercetin derivatives with target proteins. Multispectral spectroscopy and molecular simulations can reveal hydroxyl substitution effects on flavonoid-HSA binding. Thermodynamic parameters of flavonoid-DNA binding can be measured using spectroscopic methods.
Structural and computational approaches
Molecular simulations provide mechanistic insights into flavonoid binding, as shown for HSA. The molecular basis of flavonoid binding to NodD has been elucidated using structural and biochemical techniques.
Genetic and genomic methods
CRISPR knockout, point mutation, knock-in, and overexpression cell models enable functional dissection of genes involved in flavonoid binding. RNA-seq can identify transcriptional changes upon flavonoid treatment. CRISPR library screening can identify novel flavonoid-binding regulators.
Pharmacological and physiological assays
Flavonoid binding to GABA(A) receptors can be assessed using receptor binding assays and anxiolytic behavioral tests. Flavonoid-HSA binding can be studied using fluorescence quenching and equilibrium dialysis [5,6].
How CRISPR Can Be Used to Study GO:0097243 flavonoid binding
Knockout
CRISPR knockout cell models can be used to delete genes encoding candidate flavonoid-binding proteins, such as GABA(A) receptor subunits or HSA, to assess loss of flavonoid binding and downstream effects [7,5].
Point Mutation
Point mutations can be introduced into the flavonoid-binding pocket to test the role of specific residues in binding affinity, as informed by structural studies [1,6].
Knock-in
Knock-in of tagged versions of flavonoid-binding proteins (e.g., GFP or HA tags) allows pull-down and localization studies to confirm binding in vivo.
Overexpression
Overexpression of flavonoid-binding proteins can enhance cellular responses to flavonoids, useful for studying signaling pathways and drug responses [2,3].
How EDITGENE Supports flavonoid binding Research
Researchers studying flavonoid binding-related genes often need to determine whether a candidate gene is causally involved in flavonoid recognition and downstream biology. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such functional studies.
Contact EDITGENE today to design your custom CRISPR model for flavonoid binding research.
Frequently Asked Questions About flavonoid binding
What is flavonoid binding?
Flavonoid binding (GO:0097243) is a molecular function defined as binding to a flavonoid, a compound containing two or more aromatic rings, each bearing at least one aromatic hydroxyl and connected with a carbon bridge.
What genes are involved in flavonoid binding?
Genes such as NodD, CPK27, HY5, CtMYB1, and HSA encode proteins that bind flavonoids or regulate flavonoid-related processes [1,2,3,5].
How is flavonoid binding studied?
Flavonoid binding is studied using biochemical assays, flavonoid probes, multispectral spectroscopy, molecular simulations, and CRISPR-based genetic models [4,6,8].
What is the role of flavonoid binding in plants?
In plants, flavonoid binding mediates rhizobial NodD activation for symbiosis, cold tolerance via CPK27-HY5, and regulation of flavonoid biosynthesis by CtMYB1.
Does flavonoid binding affect human health?
Yes, flavonoid binding to human serum albumin affects pharmacokinetics [5,6], and binding to GABA(A) receptors is associated with anxiolytic effects.
What is the GO ID for flavonoid binding?
The GO ID for flavonoid binding is GO:0097243.
What are the synonyms for flavonoid binding?
There are no synonyms listed for GO:0097243.
Which proteins bind flavonoids?
Proteins such as NodD, human serum albumin, GABA(A) receptor, and transcription factors like HY5 and CtMYB1 bind flavonoids or are involved in flavonoid-related processes [1,5,7,2,3].
How can CRISPR help study flavonoid binding?
CRISPR knockout, point mutation, knock-in, and overexpression models enable functional dissection of genes encoding flavonoid-binding proteins.
What services does EDITGENE offer for flavonoid binding research?
EDITGENE offers knockout, point mutation, knock-in, overexpression cell models, CRISPR library screening, and bioinformatics services.
Conclusion
Flavonoid binding (GO:0097243) is a fundamental molecular function with broad biological significance, from plant-microbe symbiosis to human drug interactions. The cited literature highlights diverse proteins and mechanisms, including NodD activation, CPK27-HY5 signaling, CtMYB1 regulation, HSA binding [5,6], and GABA(A) receptor modulation. Researchers can leverage CRISPR-based models and biochemical assays to further dissect flavonoid binding mechanisms. EDITGENE provides comprehensive services to accelerate such studies.
References
- 1. Ruan Y et al.. 2026. The molecular basis of the binding and specific activation of rhizobial NodD by flavonoids.. Science 391(6781):184-189 PMID: 41505558
- 2. Lin R et al.. 2025. CPK27 enhances cold tolerance by promoting flavonoid biosynthesis through phosphorylating HY5 in tomato.. New Phytol 246(5):2174-2191 PMID: 40235338
- 3. Zhou Y et al.. 2025. CtMYB1 regulates flavonoid biosynthesis in safflower flower by binding the CAACCA elements.. PLoS One 20(12):e0337921 PMID: 41370262
- 4. Tsuchiya A et al.. 2022. Development of flavonoid probes and the binding mode of the target protein and quercetin derivatives.. Bioorg Med Chem 68:116854 PMID: 35667156
- 5. Bolli A et al.. 2010. Flavonoid binding to human serum albumin.. Biochem Biophys Res Commun 398(3):444-9 PMID: 20599706
- 6. Zhao Z et al.. 2025. Hydroxyl substitution patterns affect flavonoid-HSA binding: Mechanistic insights from multispectral spectroscopy and molecular simulations.. Food Chem 496(Pt 3):146803 PMID: 41175619
- 7. Liu Z et al.. 2021. Flavonoid compounds isolated from Tibetan herbs, binding to GABA(A) receptor with anxiolytic property.. J Ethnopharmacol 267:113630 PMID: 33246118
- 8. Janjua NK et al.. 2011. Flavonoid-DNA binding studies and thermodynamic parameters.. Spectrochim Acta A Mol Biomol Spectrosc 79(5):1600-4 PMID: 21715223
