ArticleProceedings of the National Academy of Sciences of the United States of America2003
The substrate specificity-determining amino acid code of 4-coumarate:CoA ligase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66 citing papers in PubMed, 169 citations in OpenAlex.
- Molecular Cloning, Biochemical Characterization, and Structural Insights into a Flavonoid-Associated Class II 4-Coumarate:CoA Ligase fromJournal of microbiology and biotechnology · 2026Article
- A Scots pine 4-coumarate:CoA ligase with high cinnamic acid affinity is the primary candidate for pinosylvin biosynthesis.The Plant journal : for cell and molecular biology · 2026Article
- Characterization ofPlants (Basel, Switzerland) · 2025Article
- Genome-Wide Identification Analysis of the 4-Coumarate: Coa Ligase (4CL) Gene Family inPlants (Basel, Switzerland) · 2025Article
- Designing a highly efficient type III polyketide whole-cell catalyst with minimized byproduct formation.Biotechnology for biofuels and bioproducts · 2024Article
- Integrative analysis of the metabolome and transcriptome provides insights into the mechanisms of lignan biosynthesis in Herpetospermum pedunculosum (Cucurbitaceae).BMC genomics · 2024Article
- Genome-wide identification analysis of the 4-Coumarate: CoA ligase (4CL) gene family expression profiles in Juglans regia and its wild relatives J. Mandshurica resistance and salt stress.BMC plant biology · 2024Article
- Developmental dynamic transcriptome and systematic analysis reveal the major genes underlying isoflavone accumulation in soybean.Frontiers in plant science · 2023Article
- A fungal NRPS-PKS enzyme catalyses the formation of the flavonoid naringenin.Nature communications · 2022Article
- Transcriptome sequencing and differential expression analysis of natural and BTH-treated wound healing in potato tubers (Solanum tuberosum L.).BMC genomics · 2022Article
- Applying biochemical and structural characterization of hydroxycinnamate catabolic enzymes from soil metagenome for lignin valorization strategies.Applied microbiology and biotechnology · 2022Article
- Systematic Analysis and Expression Profiles of the 4-Coumarate: CoA Ligase (4CL) Gene Family in Pomegranate (International journal of molecular sciences · 2022Article
- Suberin Biosynthesis, Assembly, and Regulation.Plants (Basel, Switzerland) · 2022Review
- Comparative Molecular Mechanisms of Biosynthesis of Naringenin and Related Chalcones in Actinobacteria and Plants: Relevance for the Obtention of Potent Bioactive Metabolites.Antibiotics (Basel, Switzerland) · 2022Review
- Article
- Specific Flavonoids and Their Biosynthetic Pathway inFrontiers in plant science · 2022Review
- Engineered biosynthesis of plant polyketides by type III polyketide synthases in microorganisms.Frontiers in bioengineering and biotechnology · 2022Review
- Genome-wide analysis of general phenylpropanoid and monolignol-specific metabolism genes in sugarcane.Functional & integrative genomics · 2021Article
- Phenolic metabolism in the hornwort Anthoceros agrestis: 4-coumarate CoA ligase and 4-hydroxybenzoate CoA ligase.Plant cell reports · 2020Article
- Characterization of the Gh4CL gene family reveals a role of Gh4CL7 in drought tolerance.BMC plant biology · 2020Article
6 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To reveal the structural principles determining substrate specificity of 4-coumarate:CoA ligase (4CL), the crystal structure of the phenylalanine activation domain of gramicidin S synthetase was used as a template for homology modeling. According to our model, 12 amino acid residues lining the Arabidopsis 4CL isoform 2 (At4CL2) substrate binding pocket (SBP) function as a signature motif generally determining 4CL substrate specificity. We used this substrate specificity code to create At4CL2 gain-of-function mutants. By increasing the space within the SBP we generated ferulic- and sinapic acid-activating At4CL2 variants. Increasing the hydrophobicity of the SBP resulted in At4CL2 variants with strongly enhanced conversion of cinnamic acid. These enzyme variants are suitable tools for investigating and influencing metabolic channeling mediated by 4CL. Knowledge of the 4CL specificity code will facilitate the prediction of substrate preference of numerous, still uncharacterized 4CL-like proteins.
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