ArticleBioscience reports2012
Allosteric modulation of caspase 3 through mutagenesis.
Article in Bioscience reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- A histidine switch regulates pH-dependent filament formation by the caspase-9 CARD.bioRxiv : the preprint server for biology · 2025Article
- Structure-Based Design and Biological Evaluation of Novel Caspase-2 Inhibitors Based on the Peptide AcVDVAD-CHO and the Caspase-2-Mediated Tau Cleavage Sequence YKPVD314.ACS pharmacology & translational science · 2022Article
- Modifications to a common phosphorylation network provide individualized control in caspases.The Journal of biological chemistry · 2018Article
- Kaempferol mitigates Endoplasmic Reticulum Stress Induced Cell Death by targeting caspase 3/7.Scientific reports · 2018Article
- Phage display and structural studies reveal plasticity in substrate specificity of caspase-3a from zebrafish.Protein science : a publication of the Protein Society · 2016Article
- 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
- What Mutagenesis Can and Cannot Reveal About Allostery.Biophysical journal · 2016Review
- Small Molecule Active Site Directed Tools for Studying Human Caspases.Chemical reviews · 2015Review
- Modifying caspase-3 activity by altering allosteric networks.Biochemistry · 2014Article
- Specificity of a protein-protein interface: local dynamics direct substrate recognition of effector caspases.Proteins · 2014Article
- Structural analysis of asparaginyl endopeptidase reveals the activation mechanism and a reversible intermediate maturation stage.Cell research · 2014Article
- A multipronged approach for compiling a global map of allosteric regulation in the apoptotic caspases.Methods in enzymology · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
A mutation in the allosteric site of the caspase 3 dimer interface of Val266 to histidine abolishes activity of the enzyme, and models predict that the mutation mimics the action of small molecule allosteric inhibitors by preventing formation of the active site. Mutations were coupled to His266 at two sites in the interface, E124A and Y197C. We present results from X-ray crystallography, enzymatic activity and molecular dynamics simulations for seven proteins, consisting of single, double and triple mutants. The results demonstrate that considering allosteric inhibition of caspase 3 as a shift between discrete 'off-state' or 'on-state' conformations is insufficient. Although His266 is accommodated in the interface, the structural defects are propagated to the active site through a helix on the protein surface. A more comprehensive view of allosteric regulation of caspase 3 requires the representation of an ensemble of inactive states and shows that subtle structural changes lead to the population of the inactive ensemble.
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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.