ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structural insight into the molecular mechanism of allosteric activation of human cystathionine β-synthase by S-adenosylmethionine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 104 citations in OpenAlex.
- Association of Cystathionine β-Synthase Gene Polymorphisms With Preeclampsia.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018Trial
- Structural basis for a filamentous morpheein model of human cystathionine beta-synthase.Nature communications · 2026Article
- Hydrogen sulfide alleviates hyperoxia effects on mitochondria in human developing airway smooth muscle.JCI insight · 2026Article
- Enzymes that generate and regulate intracellular persulfides and polysulfides: mechanistic insights and inhibitors.Frontiers in physiology · 2026Review
- Structural basis for the inhibition of cystathionine-β-synthase by isoflurane and its role in anaesthesia-induced social dysfunction in mice.British journal of anaesthesia · 2025Article
- One carbon metabolism supplementation in maturation medium but not embryo culture medium improves the yield of blastocysts from bovine oocytes.Scientific reports · 2025Article
- Impact of Varicocele on The Expression of Testicular Enzymes Involved in The Transsulfuration Pathway.International journal of fertility & sterility · 2025Article
- Impact of primary sequence changes on the self-association properties of mammalian cystathionine beta-synthase enzymes.Protein science : a publication of the Protein Society · 2024Article
- Cellular turnover and degradation of the most common missense cystathionine beta-synthase variants causing homocystinuria.Protein science : a publication of the Protein Society · 2024Article
- Specific Mutations Reverse Regulatory Effects of Adenosine Phosphates and Increase Their Binding Stoichiometry in CBS Domain-Containing Pyrophosphatase.International journal of molecular sciences · 2024Article
- Architecture and regulation of filamentous human cystathionine beta-synthase.Nature communications · 2024Article
- Effects of Streptozotocin Induced Diabetes on One-Carbon Cycle and Sperm Function.Cell journal · 2024Article
- Role of Hydrogen Sulfide in Oncological and Non-Oncological Disorders and Its Regulation by Non-Coding RNAs: A Comprehensive Review.Non-coding RNA · 2024Review
- Disease-causing cystathionine β-synthase linker mutations impair allosteric regulation.The Journal of biological chemistry · 2023Article
- Metabolic Interaction Between Folate, Vitamin B12, and Polyunsaturated Fatty Acids in Pregnancy.Advances in experimental medicine and biology · 2023Article
- Insights into Domain Organization and Regulatory Mechanism of Cystathionine Beta-Synthase fromInternational journal of molecular sciences · 2022Article
- HCellular and molecular life sciences : CMLS · 2022Article
- How to fix a broken protein: restoring function to mutant human cystathionine β-synthase.Human genetics · 2022Review
- Article
- Modulation of Human Hydrogen Sulfide Metabolism by Micronutrients, Preliminary Data.Nutrition and metabolic insights · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Cystathionine β-synthase (CBS) is a heme-dependent and pyridoxal-5'-phosphate-dependent protein that controls the flux of sulfur from methionine to cysteine, a precursor of glutathione, taurine, and H2S. Deficiency of CBS activity causes homocystinuria, the most frequent disorder of sulfur amino acid metabolism. In contrast to CBSs from lower organisms, human CBS (hCBS) is allosterically activated by S-adenosylmethionine (AdoMet), which binds to the regulatory domain and triggers a conformational change that allows the protein to progress from the basal toward the activated state. The structural basis of the underlying molecular mechanism has remained elusive so far. Here, we present the structure of hCBS with bound AdoMet, revealing the activated conformation of the human enzyme. Binding of AdoMet triggers a conformational change in the Bateman module of the regulatory domain that favors its association with a Bateman module of the complementary subunit to form an antiparallel CBS module. Such an arrangement is very similar to that found in the constitutively activated insect CBS. In the presence of AdoMet, the autoinhibition exerted by the regulatory region is eliminated, allowing for improved access of substrates to the catalytic pocket. Based on the availability of both the basal and the activated structures, we discuss the mechanism of hCBS activation by AdoMet and the properties of the AdoMet binding site, as well as the responsiveness of the enzyme to its allosteric regulator. The structure described herein paves the way for the rational design of compounds modulating hCBS activity and thus transsulfuration, redox status, and H2S biogenesis.
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