ArticleThe Journal of biological chemistry2011
Structural basis of multifunctionality in a vitamin B12-processing enzyme.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 90 citations in OpenAlex.
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- An unusual Co-S bond links BProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The cobalamin processing enzyme of Trichoplax adhaerens.The Journal of biological chemistry · 2025Article
- Ultrafast X-ray Absorption Spectroscopy Reveals Excited-State Dynamics of BThe journal of physical chemistry. B · 2024Article
- Interaction of Glutathione with MMACHC Arginine-Rich Pocket Variants Associated with Cobalamin C Disease: Insights from Molecular Modeling.Biomedicines · 2023Article
- Cobalt-Sulfur Coordination Chemistry Drives BJournal of the American Chemical Society · 2023Article
- meso-Bromination of cyano- and aquacobalamins facilitates their processing into Co(II)-species by glutathione.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023Article
- Riboflavin: a scoping review for Nordic Nutrition Recommendations 2023.Food & nutrition research · 2023Article
- Versatile enzymology and heterogeneous phenotypes in cobalamin complementation type C disease.iScience · 2022Review
- Bioprocess Strategies for Vitamin BBioengineering (Basel, Switzerland) · 2022Review
- Mutations in Hcfc1 and Ronin result in an inborn error of cobalamin metabolism and ribosomopathy.Nature communications · 2022Article
- The human BMethods in enzymology · 2022Article
- Surprising Homolytic Gas Phase Co-C Bond Dissociation Energies of Organometallic Aryl-Cobinamides Reveal Notable Non-Bonded Intramolecular Interactions.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Redox-Linked Coordination Chemistry Directs Vitamin BAccounts of chemical research · 2021Article
- Mobile loop dynamics in adenosyltransferase control binding and reactivity of coenzyme BProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Chlorocob(II)alamin Formation Which Enhances the Thiol Oxidase Activity of the BInorganic chemistry · 2020Article
- Vitamin B12 may inhibit RNA-dependent-RNA polymerase activity of nsp12 from the SARS-CoV-2 virus.IUBMB life · 2020Article
- An Interprotein Co-S Coordination Complex in the BJournal of the American Chemical Society · 2020Article
- The human BThe Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
An early step in the intracellular processing of vitamin B(12) involves CblC, which exhibits dual reactivity, catalyzing the reductive decyanation of cyanocobalamin (vitamin B(12)), and the dealkylation of alkylcobalamins (e.g. methylcobalamin; MeCbl). Insights into how the CblC scaffold supports this chemical dichotomy have been unavailable despite it being the most common locus of patient mutations associated with inherited cobalamin disorders that manifest in both severe homocystinuria and methylmalonic aciduria. Herein, we report structures of human CblC, with and without bound MeCbl, which provide novel biochemical insights into its mechanism of action. Our results reveal that CblC is the most divergent member of the NADPH-dependent flavin reductase family and can use FMN or FAD as a prosthetic group to catalyze reductive decyanation. Furthermore, CblC is the first example of an enzyme with glutathione transferase activity that has a sequence and structure unrelated to the GST superfamily. CblC thus represents an example of evolutionary adaptation of a common structural platform to perform diverse chemistries. The CblC structure allows us to rationalize the biochemical basis of a number of pathological mutations associated with severe clinical phenotypes.
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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.