ArticleThe Journal of biological chemistry2009
Structural and mechanistic studies reveal the functional role of bicovalent flavinylation in berberine bridge enzyme.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 49 citations in OpenAlex.
- Structural and biochemical basis for cannabinoid cyclase activity in marine bacterial flavoenzymes.Nature chemical biology · 2026Article
- Oomycetes manipulate plant innate immunity through galacturonide oxidases.Nature communications · 2025Article
- Structural and biochemical basis for cannabinoid cyclase activity in marine bacterial flavoenzymes.bioRxiv : the preprint server for biology · 2025Article
- Discovery of Latent Cannabichromene Cyclase Activity in Marine Bacterial Flavoenzymes.ACS synthetic biology · 2024Article
- Rethinking Biosynthesis of Aclacinomycin A.Molecules (Basel, Switzerland) · 2023Review
- HarnessingJournal of natural products · 2022Review
- Berberine bridge enzyme-like oxidase-catalysed double bond isomerization acts as the pathway switch in cytochalasin synthesis.Nature communications · 2022Article
- Discovery of fungal oligosaccharide-oxidising flavo-enzymes with previously unknown substrates, redox-activity profiles and interplay with LPMOs.Nature communications · 2021Article
- Oxidative Cyclization in Natural Product Biosynthesis.Chemical reviews · 2017Review
- Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides.Beilstein journal of organic chemistry · 2016Review
- Structure of a Berberine Bridge Enzyme-Like Enzyme with an Active Site Specific to the Plant Family Brassicaceae.PloS one · 2016Article
- Oxidation of Monolignols by Members of the Berberine Bridge Enzyme Family Suggests a Role in Plant Cell Wall Metabolism.The Journal of biological chemistry · 2015Article
- The important ergot alkaloid intermediate chanoclavine-I produced in the yeast Saccharomyces cerevisiae by the combined action of EasC and EasE from Aspergillus japonicus.Microbial cell factories · 2014Article
- The role of biocatalysis in the asymmetric synthesis of alkaloids.RSC advances · 2013Review
- Asymmetric Preparation ofOrganic process research & development · 2013Article
- Catalytic and structural role of a conserved active site histidine in berberine bridge enzyme.Biochemistry · 2012Article
- Biocatalytic organic synthesis of optically pure (S)-scoulerine and berbine and benzylisoquinoline alkaloids.The Journal of organic chemistry · 2011Article
- Tirandamycin biosynthesis is mediated by co-dependent oxidative enzymes.Nature chemistry · 2011Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Berberine bridge enzyme (BBE) is a member of the recently discovered family of bicovalently flavinylated proteins. In this group of enzymes, the FAD cofactor is linked via its 8alpha-methyl group and the C-6 atom to conserved histidine and cysteine residues, His-104 and Cys-166 for BBE, respectively. 6-S-Cysteinylation has recently been shown to have a significant influence on the redox potential of the flavin cofactor; however, 8alpha-histidylation evaded a closer characterization due to extremely low expression levels upon substitution. Co-overexpression of protein disulfide isomerase improved expression levels and allowed isolation and purification of the H104A protein variant. To gain more insight into the functional role of the unusual dual mode of cofactor attachment, we solved the x-ray crystal structures of two mutant proteins, H104A and C166A BBE, each lacking one of the covalent linkages. Information from a structure of wild type enzyme in complex with the product of the catalyzed reaction is combined with the kinetic and structural characterization of the protein variants to demonstrate the importance of the bicovalent linkage for substrate binding and efficient oxidation. In addition, the redox potential of the flavin cofactor is enhanced additively by the dual mode of cofactor attachment. The reduced level of expression for the H104A mutant protein and the difficulty of isolating even small amounts of the protein variant with both linkages removed (H104A-C166A) also points toward a possible role of covalent flavinylation during protein folding.
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.