Evidence map›Paper›PMID 38575566›Full record

ArticleNature communications2024

Architecture and regulation of filamentous human cystathionine beta-synthase.

Thomas J McCorvie, Douglas Adamoski, Raquel A C Machado, Jiazhi Tang, Henry J Bailey, Douglas S M Ferreira, Claire Strain-Damerell, Arnaud Baslé, Andre L B Ambrosio, Sandra M G Dias and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Glutamine metabolic enzymes: to filament or not to filament?Biochemical Society transactions · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 3 countries.

Thomas J McCorvieNuffield Department of Clinical Medicine, Centre for Medicines Discovery, University of Oxford, Oxford, OX3 7DQ, UK. thomas.mccorvie@newcastle.ac.uk.ORCID http://orcid.org/0000-0002-1502-7113
Douglas AdamoskiBrazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, 13083-970, Campinas, Brazil.ORCID http://orcid.org/0000-0001-5062-2586
Raquel A C MachadoBrazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, 13083-970, Campinas, Brazil.ORCID http://orcid.org/0000-0001-5912-2991
Jiazhi TangBiosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Henry J BaileyNuffield Department of Clinical Medicine, Centre for Medicines Discovery, University of Oxford, Oxford, OX3 7DQ, UK.
Douglas S M FerreiraNuffield Department of Clinical Medicine, Centre for Medicines Discovery, University of Oxford, Oxford, OX3 7DQ, UK.
Claire Strain-DamerellNuffield Department of Clinical Medicine, Centre for Medicines Discovery, University of Oxford, Oxford, OX3 7DQ, UK.ORCID http://orcid.org/0000-0003-4964-2090
Arnaud BasléBiosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Andre L B AmbrosioSao Carlos Institute of Physics, University of Sao Paulo, Sao Carlos, SP, Brazil.ORCID http://orcid.org/0000-0002-9515-930X
Sandra M G DiasBrazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, 13083-970, Campinas, Brazil.ORCID http://orcid.org/0000-0002-1589-7856
Wyatt W YueNuffield Department of Clinical Medicine, Centre for Medicines Discovery, University of Oxford, Oxford, OX3 7DQ, UK. wyatt.yue@newcastle.ac.uk.ORCID http://orcid.org/0000-0001-6959-6007
University of Oxford · GBBrazilian Center for Research in Energy and Materials · BRNewcastle University · GBGoethe University Frankfurt · DEUniversidade Federal de São Carlos · BR

Funding

Wellcome Trust
6 · The paper itself

Abstract

Cystathionine beta-synthase (CBS) is an essential metabolic enzyme across all domains of life for the production of glutathione, cysteine, and hydrogen sulfide. Appended to the conserved catalytic domain of human CBS is a regulatory domain that modulates activity by S-adenosyl-L-methionine (SAM) and promotes oligomerisation. Here we show using cryo-electron microscopy that full-length human CBS in the basal and SAM-bound activated states polymerises as filaments mediated by a conserved regulatory domain loop. In the basal state, CBS regulatory domains sterically block the catalytic domain active site, resulting in a low-activity filament with three CBS dimers per turn. This steric block is removed when in the activated state, one SAM molecule binds to the regulatory domain, forming a high-activity filament with two CBS dimers per turn. These large conformational changes result in a central filament of SAM-stabilised regulatory domains at the core, decorated with highly flexible catalytic domains. Polymerisation stabilises CBS and reduces thermal denaturation. In PC-3 cells, we observed nutrient-responsive CBS filamentation that disassembles when methionine is depleted and reversed in the presence of SAM. Together our findings extend our understanding of CBS enzyme regulation, and open new avenues for investigating the pathogenic mechanism and therapeutic opportunities for CBS-associated disorders.

Indexed as

Cystathionine beta-SynthaseMethionineCatalytic DomainCryoelectron MicroscopyHumansS-AdenosylmethionineCystathionine beta-SynthaseMethionineS-Adenosylmethionine

Identifiers

PMID38575566
PMCPMC10995199
OpenAlexW4393929526

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.