ArticleThe Journal of biological chemistry2012
Inhibitory mechanism of caspase-6 phosphorylation revealed by crystal structures, molecular dynamics simulations, and biochemical assays.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- The Intricate Role of Caspase-6 and Death Receptor-6 in Neurodegenerative Diseases.Cell biochemistry and biophysics · 2026Review
- An NMR sample preparation case study: Considerations for the self-destructive protease caspase-6.PloS one · 2025Article
- How does caspases regulation play role in cell decisions? apoptosis and beyond.Molecular and cellular biochemistry · 2024Review
- Non-Canonical Roles of Apoptotic Caspases in the Nervous System.Frontiers in cell and developmental biology · 2022Review
- Role of ARK5 in cancer and other diseases (Review).Experimental and therapeutic medicine · 2021Review
- Recent advances suggest increased influence of selective pressure in allostery.Current opinion in structural biology · 2020Review
- Activation of Caspase-6 Is Promoted by a Mutant Huntingtin Fragment and Blocked by an Allosteric Inhibitor Compound.Cell chemical biology · 2019Article
- Identification of Allosteric Inhibitors against Active Caspase-6.Scientific reports · 2019Article
- Rare human Caspase-6-R65W and Caspase-6-G66R variants identify a novel regulatory region of Caspase-6 activity.Scientific reports · 2018Article
- Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Modifying caspase-3 activity by altering allosteric networks.Biochemistry · 2014Article
- A multipronged approach for compiling a global map of allosteric regulation in the apoptotic caspases.Methods in enzymology · 2014Article
- Structural snapshots reveal distinct mechanisms of procaspase-3 and -7 activation.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Computational study of the effects of protein tyrosine nitrations on the catalytic activity of human thymidylate synthase.Journal of computer-aided molecular design · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The apoptotic effector caspase-6 (CASP6) has been clearly identified as a drug target due to its strong association with neurodegeneration and axonal pruning events as well as its crucial roles in Huntington disease and Alzheimer disease. CASP6 activity is suppressed by ARK5-mediated phosphorylation at Ser(257) with an unclear mechanism. In this work, we solved crystal structures of ΔproCASP6S257E and p20/p10S257E, which mimicked the phosphorylated CASP6 zymogen and activated CASP6, respectively. The structural investigation combined with extensive biochemical assay and molecular dynamics simulation studies revealed that phosphorylation on Ser(257) inhibited self-activation of CASP6 zymogen by "locking" the enzyme in the TEVD(193)-bound "inhibited state." The structural and biochemical results also showed that phosphorylation on Ser(257) inhibited the CASP6 activity by steric hindrance. These results disclosed the inhibition mechanism of CASP6 phosphorylation and laid the foundation for a new strategy of rational CASP6 drug design.
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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.