Evidence map›Paper›PMID 42918798›Full record

ArticleNature communications2026

Hydrogen sulfide engages catalytic zinc in HDAC6 to modulate an alternative deacetylation pathway.

Chen Sun, Yin-Fang Wang, Sheng-Yang Cai, Kui-Fang Xie, Jia-Qi Zhu, Xue-Pan Mu, Zhi-Ni Zhu, Yu-Lin Chao, Zi-Xuan Zhou, Xi-Qing Bian and 14 more

Abstract read
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In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

24 authors.

Chen SunShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.ORCID http://orcid.org/0009-0009-6998-7070
Yin-Fang WangShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.
Sheng-Yang CaiShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.ORCID http://orcid.org/0009-0006-7341-7802
Kui-Fang XieShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.
Jia-Qi ZhuShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.
Xue-Pan MuShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.
Zhi-Ni ZhuEye & ENT Hospital, Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Department of Systems Biology for Medicine, Fudan University, Shanghai, China.
Yu-Lin ChaoCentral Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Zi-Xuan ZhouEye & ENT Hospital, Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Department of Systems Biology for Medicine, Fudan University, Shanghai, China.
Xi-Qing BianLaboratory of Drug Discovery from Natural Resources and Industrialization and School of Pharmacy, Macau University of Science and Technology; Avenida WaiLong, Taipa, Macau, China.ORCID http://orcid.org/0000-0003-2319-2271
Wen MiaoLaboratory of Drug Discovery from Natural Resources and Industrialization and School of Pharmacy, Macau University of Science and Technology; Avenida WaiLong, Taipa, Macau, China.
Jian-Lin WuLaboratory of Drug Discovery from Natural Resources and Industrialization and School of Pharmacy, Macau University of Science and Technology; Avenida WaiLong, Taipa, Macau, China.ORCID http://orcid.org/0000-0002-3875-185X
Jingwei WengDepartment of Chemistry, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-4639-7600
Ying ChenShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.
Wen-Long XueShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.
Meng-Yao LiShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.
Ai-Qiu ChiShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.
Qian DingLaboratory of Drug Discovery from Natural Resources and Industrialization and School of Pharmacy, Macau University of Science and Technology; Avenida WaiLong, Taipa, Macau, China.
Ming-Jie WangShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.
Bei-Bei TaoShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China.
Igor Ying ZhangDepartment of Chemistry, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-8703-1912
Yi Zhun ZhuLaboratory of Drug Discovery from Natural Resources and Industrialization and School of Pharmacy, Macau University of Science and Technology; Avenida WaiLong, Taipa, Macau, China. yzzhu@must.edu.mo.ORCID http://orcid.org/0000-0001-7700-8041
Qian-Hui QuEye & ENT Hospital, Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Department of Systems Biology for Medicine, Fudan University, Shanghai, China. qqh@fudan.edu.cn.ORCID http://orcid.org/0000-0002-5753-2599
Yi-Chun ZhuShanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China. yczhu@shmu.edu.cn.ORCID http://orcid.org/0000-0002-0873-2957

Funding

National Natural Science Foundation of China (National Science Foundation of China) 31830042National Natural Science Foundation of China (National Science Foundation of China) 32371227
6 · The paper itself

Abstract

Hydrogen sulfide (H₂S) is a gasotransmitter whose non-covalent effects on protein function remain incompletely understood. Here we show that H₂S-derived sulfur species engage the catalytic Zn²⁺ center of histone deacetylase 6 (HDAC6) and enhance deacetylase activity under defined conditions. Molecular dynamics simulations support access of HS⁻ to the CD2 active-site tunnel, whereas surface plasmon resonance and zinc-depletion experiments support reversible, zinc-dependent engagement. Quantum chemical calculations support a chemically feasible sulfur-associated deacetylation pathway that generates thioacetic acid, which we detect in cell-free reactions, cultured cells, mouse tissues and human serum. Cryo-electron microscopy defines the tandem organization of human HDAC6 catalytic domains and reveals distinct CD1 and CD2 tunnel architectures. HDAC6 loss blunts H₂S-induced endothelial migration and angiogenesis, and CD2 is required for these responses. These findings support HDAC6 as an H₂S-responsive Zn²⁺-dependent deacetylase and link zinc-sulfur coordination to altered deacetylation chemistry.

Indexed as

Histone Deacetylase 6Histone DeacetylasesHydrogen SulfideZincAcetylationAnimalsCatalytic DomainCell MovementHumansMiceMolecular Dynamics SimulationNeovascularization, PhysiologicHDAC6 protein, humanHistone Deacetylase 6Histone DeacetylasesHydrogen SulfideZinc

Identifiers

PMID42918798

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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.