The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Structural insights into HDAC6 tubulin deacetylation and its selective inhibition
Abstract
We report crystal structures of zebrafish histone deacetylase 6 (HDAC6) catalytic domains in tandem or as single domains in complex with the (R) and (S) enantiomers of trichostatin A (TSA) or with the HDAC6-specific inhibitor nexturastat A. The tandem domains formed, together with the inter-domain linker, an ellipsoid-shaped complex with pseudo-twofold symmetry. We identified important active site differences between both catalytic domains and revealed the binding mode of HDAC6 selective inhibitors. HDAC inhibition assays with (R)- and (S)-TSA showed that (R)-TSA was a broad-range inhibitor, whereas (S)-TSA had moderate selectivity for HDAC6. We identified a uniquely positioned α-helix and a flexible tryptophan residue in the loop joining α-helices H20 to H21 as critical for deacetylation of the physiologic substrate tubulin. Using single-molecule measurements and biochemical assays we demonstrated that HDAC6 catalytic domain 2 deacetylated α-tubulin lysine 40 in the lumen of microtubules, but that its preferred substrate was unpolymerized tubulin.
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“Selective inhibition appears to rely on small structural differences between HDAC1-3 and HDAC6 and on small thermodynamic differences in selective inhibitor binding 42-46 .”
From Characterization of Histone Deacetylase 8 (HDAC8) Selective Inhibition Reveals Specific Active Site Structural and Functional Determinants (2018) · cites this paper as [44]
In the citing paper
“the recent work on HDAC6/inhibitor complexes demonstrate that L1 loop conformational stability is important for the interactions of L1 loop residues with inhibitors capping groups to achieve HDAC6 selectivity inhibition 42-46”
From Characterization of Histone Deacetylase 8 (HDAC8) Selective Inhibition Reveals Specific Active Site Structural and Functional Determinants (2018) · cites this paper as [44]
In the citing paper
“HDAC10 PDAC-ΨDAC heterodomain assembly resembles HDAC6 heterodomain assembly and HDAC homodomain assembly in Schizosaccharomyces pombe Clr3 (Supplementary Fig. 5)2728.”
From Histone deacetylase 10 structure and molecular function as a polyamine deacetylase (2017) · cites this paper as [27]
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Cites
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
Kabsch, W. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909047337 · Cited by 16,463
Towards automated crystallographic structure refinement with phenix.refine
Afonine, P. V., Grosse-Kunstleve, R. W., Echols, N., Headd, J. J., Moriarty, N. W., Mustyakimov, M., Terwilliger, T. C., Urzhumtsev, A., Zwart, P. H., & Adams, P. D. (2012) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444912001308 · Cited by 5,511
The HHpred interactive server for protein homology detection and structure prediction
Söding, J., Biegert, A., & Lupas, A. N. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki408 · Cited by 3,775
Comparative Protein Structure Modeling of Genes and Genomes
Martí-Renom, M. A., Stuart, A. C., Fiser, A., Sánchez, R., Melo, F., & Šali, A. (2000) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.29.1.291 · Cited by 3,169
HDAC6 is a microtubule-associated deacetylase
Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Wang, X.-F., & Yao, T.-P. (2002) · Nature · doi:10.1038/417455a · Cited by 2,403
Self-citationData processing and analysis with the autoPROC toolbox
Vonrhein, C., Flensburg, C., Keller, P., Sharff, A., Smart, O. S., Paciorek, W. A., Womack, T. O., & Bricogne, G. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444911007773 · Cited by 2,084
Yoshida, M., Kijima, M., Akita, M., & Beppu, T. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44885-x · Cited by 1,856
The Buccaneer software for automated model building. 1. Tracing protein chains
Cowtan, K. D. (2006) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444906022116 · Cited by 1,834
Research works printed but not linked: 1
- Bricogne, G. et al. BUSTER version 2.11.4. (Global Phasing Ltd., Cambridge, UK, 2011).
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Magupalli, V. G., Negro, R., Tian, Y., Hauenstein, A. V., Caprio, G. D., Skillern, W., Deng, Q., Ørning, P., Alam, H. B., Maliga, Z., et al. (2020) · Science · doi:10.1126/science.aas8995 · Cited by 392
Causes and Consequences of Microtubule Acetylation
Janke, C., & Montagnac, G. (2017) · Current Biology · doi:10.1016/j.cub.2017.10.044 · Cited by 316
The Tubulin Code in Microtubule Dynamics and Information Encoding
Roll‐Mecak, A. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.06.008 · Cited by 307
Acetylation of intrinsically disordered regions regulates phase separation
Saito, M., Heß, D., Eglinger, J., Fritsch, A. W., Kreysing, M., Weinert, B. T., Choudhary, C., & Matthias, P. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0180-7 · Cited by 296
Self-citationTurbulence Activates Platelet Biogenesis to Enable Clinical Scale Ex Vivo Production
Ito, Y., Nakamura, S., Sugimoto, N., Shigemori, T., Kato, Y., Ohno, M., Sakuma, S., Ito, K., Kumon, H., Hirose, H., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.011 · Cited by 297
Metadata
- Authors
- Miyake, Y., Keusch, J. J., Wang, L., Saito, M., Hess, D., Wang, X., Melancon, B. J., Helquist, P., Gut, H., & Matthias, P.
- Affiliations
- Friedrich Miescher Institute (CH)
- University of Notre Dame (US)
- University of Basel (CH)
- Corresponding author
- Matthias, Patrick
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2016-07-25
- Volume
- 12
- Issue
- 9
- Pages
- 748-754
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2482664294
- Cited by
- 315
- References
- 58
- Citations by year
- 2026: 31 · 2025: 32 · 2024: 24 · 2023: 31 · 2022: 27 · 2021: 39 · 2020: 36 · 2019: 37 · 2018: 34 · 2017: 18 · 2016: 6
- FWCI
- 17.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS092653)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Keywords
- HDAC6, histone deacetylase, tubulin deacetylation, trichostatin A, crystal structure, enantiomers, enzyme inhibition, microtubules, active site, zebrafish
- MeSH terms
- Histone Deacetylase 6, Acetylation, Animals, Histone Deacetylases, Humans, Hydroxamic Acids, Models, Molecular, Structure-Activity Relationship, Tubulin, Zebrafish, Zebrafish Proteins, Biocatalysis, Histone Deacetylase Inhibitors
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