ArticleThe Journal of biological chemistry2014
Inter-domain communication of human cystathionine β-synthase: structural basis of S-adenosyl-L-methionine activation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Enhancing virtual screening of cystathionine β-synthase inhibitors: benchmarking target-specific machine-learning scoring functions against state-of-the-art AI docking and co-folding approaches.Journal of cheminformatics · 2026Article
- Structural basis for a filamentous morpheein model of human cystathionine beta-synthase.Nature communications · 2026Article
- A versatile method for designing biosensors via regulatory domains of allosteric enzymes.Nature communications · 2026Article
- 5,10-Methylenetetrahydrofolate Reductase─the Key Allosteric Regulator in One-Carbon Metabolism.Biochemistry · 2026Review
- IDH-mutant inhibitors enhance the sensitivity of IDH1-mutant gliomas to cysteine-methionine deprivation and ferroptosis.bioRxiv : the preprint server for biology · 2026Article
- Enzymes that generate and regulate intracellular persulfides and polysulfides: mechanistic insights and inhibitors.Frontiers in physiology · 2026Review
- Methanogenesis marker 16 metalloprotein is the primary coenzyme M synthase in Methanosarcina acetivorans.PLoS genetics · 2025Article
- 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
- Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase.Nature communications · 2024Article
- Architecture and regulation of filamentous human cystathionine beta-synthase.Nature communications · 2024Article
- Disease-causing cystathionine β-synthase linker mutations impair allosteric regulation.The Journal of biological chemistry · 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
- Analysis of S-Adenosylmethionine and S-Adenosylhomocysteine: Method Optimisation and Profiling in Healthy Adults upon Short-Term Dietary Intervention.Metabolites · 2022Article
- Cysteine metabolic circuitries: druggable targets in cancer.British journal of cancer · 2021Review
- Structural insight into the unique conformation of cystathionine β-synthase fromComputational and structural biotechnology journal · 2021Article
- Screening of Heteroaromatic Scaffolds against Cystathionine Beta-Synthase Enables Identification of Substituted Pyrazolo[3,4-c]Pyridines as Potent and Selective Orthosteric Inhibitors.Molecules (Basel, Switzerland) · 2020Article
- Review
- Hydrogen Sulfide Metabolism and Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Cystathionine β-synthase (CBS) is a key enzyme in sulfur metabolism, and its inherited deficiency causes homocystinuria. Mammalian CBS is modulated by the binding of S-adenosyl-l-methionine (AdoMet) to its regulatory domain, which activates its catalytic domain. To investigate the underlying mechanism, we performed x-ray crystallography, mutagenesis, and mass spectrometry (MS) on human CBS. The 1.7 Å structure of a AdoMet-bound CBS regulatory domain shows one AdoMet molecule per monomer, at the interface between two constituent modules (CBS-1, CBS-2). AdoMet binding is accompanied by a reorientation between the two modules, relative to the AdoMet-free basal state, to form interactions with AdoMet via residues verified by mutagenesis to be important for AdoMet binding (Phe(443), Asp(444), Gln(445), and Asp(538)) and for AdoMet-driven inter-domain communication (Phe(443), Asp(538)). The observed structural change is further supported by ion mobility MS, showing that as-purified CBS exists in two conformational populations, which converged to one in the presence of AdoMet. We therefore propose that AdoMet-induced conformational change alters the interface and arrangement between the catalytic and regulatory domains within the CBS oligomer, thereby increasing the accessibility of the enzyme active site for catalysis.
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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.