ArticleNature chemical biology2012
Allosteric peptides bind a caspase zymogen and mediate caspase tetramerization.
Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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.
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.
Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Structure of the Wnt-Frizzled-LRP6 initiation complex reveals the basis for coreceptor discrimination.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Screening of Therapeutic Peptides for Anti-Inflammation through Phage Display Technology.International journal of molecular sciences · 2022Review
- Conformational transitions of caspase-6 in substrate-induced activation process explored by perturbation-response scanning combined with targeted molecular dynamics.Computational and structural biotechnology journal · 2021Article
- 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
- A selective peptide inhibitor of Frizzled 7 receptors disrupts intestinal stem cells.Nature chemical biology · 2018Article
- Rare human Caspase-6-R65W and Caspase-6-G66R variants identify a novel regulatory region of Caspase-6 activity.Scientific reports · 2018Article
- Palmitoylation of caspase-6 by HIP14 regulates its activation.Cell death and differentiation · 2017Article
- Caspase vinyl sulfone small molecule inhibitors prevent axonal degeneration in human neurons and reverse cognitive impairment in Caspase-6-overexpressing mice.Molecular neurodegeneration · 2017Article
- Small Molecule Active Site Directed Tools for Studying Human Caspases.Chemical reviews · 2015Review
- Identification of a small peptide that inhibits PCSK9 protein binding to the low density lipoprotein receptor.The Journal of biological chemistry · 2014Article
- A multipronged approach for compiling a global map of allosteric regulation in the apoptotic caspases.Methods in enzymology · 2014Article
- Structural basis of the interaction of MbtH-like proteins, putative regulators of nonribosomal peptide biosynthesis, with adenylating enzymes.The Journal of biological chemistry · 2013Article
- Expanding the number of 'druggable' targets: non-enzymes and protein-protein interactions.Chemical biology & drug design · 2013Review
- A caspase cascade regulating developmental axon degeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Zinc-mediated allosteric inhibition of caspase-6.The Journal of biological chemistry · 2012Article
- Peptide inhibitors: Four of a kind beats a pair.Nature chemical biology · 2012Article
Corrections and comments
- Commented on by
- Erratum issuedKrylova, Irina [added]
- Erratum issued
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The caspases are a family of cytosolic proteases with essential roles in inflammation and apoptosis. Drug discovery efforts have focused on developing molecules directed against the active sites of caspases, but this approach has proved challenging and has not yielded any approved therapeutics. Here we describe a new strategy for generating inhibitors of caspase-6, a potential therapeutic target in neurodegenerative disorders, by screening against its zymogen form. Using phage display to discover molecules that bind the zymogen, we report the identification of a peptide that specifically impairs the function of caspase-6 in vitro and in neuronal cells. Remarkably, the peptide binds at a tetramerization interface that is uniquely present in zymogen caspase-6, rather than binding into the active site, and acts via a new allosteric mechanism that promotes caspase tetramerization. Our data illustrate that screening against the zymogen holds promise as an approach for targeting caspases in drug discovery.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.