ArticleProceedings of the National Academy of Sciences of the United States of America2013
Structural basis of regulation and oligomerization of human cystathionine β-synthase, the central enzyme of transsulfuration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 111 citations in OpenAlex.
- Structural basis for a filamentous morpheein model of human cystathionine beta-synthase.Nature communications · 2026Article
- Loss of cystathionine-β-synthase contributes to elevated OXPHOS, a vulnerability in Ara-C-resistant Myeloid Leukemia in Down syndrome.Biochemical pharmacology · 2026Article
- 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
- 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
- Architecture and regulation of filamentous human cystathionine beta-synthase.Nature communications · 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
- The Structure and Nucleotide-Binding Characteristics of Regulated Cystathionine β-Synthase Domain-Containing Pyrophosphatase without One Catalytic Domain.International journal of molecular sciences · 2023Article
- Disease-causing cystathionine β-synthase linker mutations impair allosteric regulation.The Journal of biological chemistry · 2023Article
- satmut_utils: a simulation and variant calling package for multiplexed assays of variant effect.Genome biology · 2023Article
- From Gasotransmitter to Immunomodulator: The Emerging Role of Hydrogen Sulfide in Macrophage Biology.Antioxidants (Basel, Switzerland) · 2023Review
- Reactive sulfur species and their significance in health and disease.Bioscience reports · 2022Review
- Sequential Accumulation of 'Driver' Pathway Mutations Induces the Upregulation of Hydrogen-Sulfide-Producing Enzymes in Human Colonic Epithelial Cell Organoids.Antioxidants (Basel, Switzerland) · 2022Article
- Article
- 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
- Structural Basis for Allostery in PLP-dependent Enzymes.Frontiers in molecular biosciences · 2022Review
- Structural perspectives on HCurrent opinion in structural biology · 2021Review
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Cystathionine β-synthase (CBS) controls the flux of sulfur from methionine to cysteine, a precursor of glutathione, taurine, and H2S. CBS condenses serine and homocysteine to cystathionine with the help of three cofactors, heme, pyridoxal-5'-phosphate, and S-adenosyl-l-methionine. Inherited deficiency of CBS activity causes homocystinuria, the most frequent disorder of sulfur metabolism. We present the structure of the human enzyme, discuss the unique arrangement of the CBS domains in the C-terminal region, and propose how they interact with the catalytic core of the complementary subunit to regulate access to the catalytic site. This arrangement clearly contrasts with other proteins containing the CBS domain including the recent Drosophila melanogaster CBS structure. The absence of large conformational changes and the crystal structure of the partially activated pathogenic D444N mutant suggest that the rotation of CBS motifs and relaxation of loops delineating the entrance to the catalytic site represent the most likely molecular mechanism of CBS activation by S-adenosyl-l-methionine. Moreover, our data suggest how tetramers, the native quaternary structure of the mammalian CBS enzymes, are formed. Because of its central role in transsulfuration, redox status, and H2S biogenesis, CBS represents a very attractive therapeutic target. The availability of the structure will help us understand the pathogenicity of the numerous missense mutations causing inherited homocystinuria and will allow the rational design of compounds modulating CBS activity.
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