ArticleBiochemistry2003
An uncleavable procaspase-3 mutant has a lower catalytic efficiency but an active site similar to that of mature caspase-3.
Article in Biochemistry, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 68 citations in OpenAlex.
- Sequential Unfolding Mechanisms of Monomeric Caspases.Biochemistry · 2023Article
- Sequential unfolding mechanisms of monomeric caspases.bioRxiv : the preprint server for biology · 2023Article
- Comparing the folding landscapes of evolutionarily divergent procaspase-3.Bioscience reports · 2022Article
- Evolution of the folding landscape of effector caspases.The Journal of biological chemistry · 2021Article
- Tracking exogenous intracellular casp-3 using split GFP.Protein science : a publication of the Protein Society · 2021Article
- Caspases from scleractinian coral show unique regulatory features.The Journal of biological chemistry · 2020Article
- Targeting apoptotic caspases in cancer.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Spatial and temporal alterations in protein structure by EGF regulate cryptic cysteine oxidation.Science signaling · 2020Article
- Resurrection of ancestral effector caspases identifies novel networks for evolution of substrate specificity.The Biochemical journal · 2019Review
- Procaspase-3 Overexpression in Cancer: A Paradoxical Observation with Therapeutic Potential.ACS chemical biology · 2019Review
- The prodomain of caspase-3 regulates its own removal and caspase activation.Cell death discovery · 2019Article
- Balance between senescence and apoptosis is regulated by telomere damage-induced association between p16 and caspase-3.The Journal of biological chemistry · 2018Article
- Modifications to a common phosphorylation network provide individualized control in caspases.The Journal of biological chemistry · 2018Article
- Allosteric Tuning of Caspase-7: A Fragment-Based Drug Discovery Approach.Angewandte Chemie (International ed. in English) · 2017Article
- Article
- 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
- Small-Molecule Procaspase-3 Activation Sensitizes Cancer to Treatment with Diverse Chemotherapeutics.ACS central science · 2016Article
- Molecular evidence of Zn chelation of the procaspase activating compound B-PAC-1 in B cell lymphoma.Oncotarget · 2016Article
- Modifying caspase-3 activity by altering allosteric networks.Biochemistry · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have examined the enzymatic activity of an uncleavable procaspase-3 mutant (D9A/D28A/D175A), which contains the wild-type catalytic residues in the active site. The results are compared to those for the mature caspase-3. Although at pH 7.5 and 25 degrees C the K(m) values are similar, the catalytic efficiency (k(cat)) is approximately 130-fold lower in the zymogen. The mature caspase-3 demonstrates a maximum activity at pH 7.4, whereas the maximum activity of procaspase-3 occurs at pH 8.3. The pK(a) values of both catalytic groups, H121 and C163, are shifted to higher pH for procaspase-3. We developed limited proteolysis assays using trypsin and V8 proteases, and we show that these assays allow the examination of amino acids in three of five active site loops. In addition, we examined the fluorescence emission of the two tryptophanyl residues in the active site over the pH range of 2.5-9 as well as the response to several quenching agents. Overall, the data suggest that the major conformational change that occurs upon maturation results in formation of the loop bundle among loops L4, L2, and L2'. The pK(a) values of both catalytic groups decrease as a result of the loop movements. However, loop L3, which comprises the bulk of the substrate binding pocket, does not appear to be unraveled and solvent-exposed, even at lower pH.
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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.