ArticleBiochemistry2006
Role of loop bundle hydrogen bonds in the maturation and activity of (Pro)caspase-3.
Article in Biochemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Caspases: structural and molecular mechanisms and functions in cell death, innate immunity, and disease.Cell discovery · 2025Review
- Investigation of the Anti-Lung Cancer Mechanisms ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Network pharmacology and experimental validation to reveal the target of matrine against PRRSV.iScience · 2023Article
- Computational screening for new neuroprotective ingredients against Alzheimer's disease from bilberry by cheminformatics approaches.Frontiers in nutrition · 2022Article
- Evolution of the folding landscape of effector caspases.The Journal of biological chemistry · 2021Article
- New pyridine and chromene scaffolds as potent vasorelaxant and anticancer agents.RSC advances · 2021Article
- Synthesis, Characterization, In Vitro Anticancer Potentiality, and Antimicrobial Activities of Novel Peptide-Glycyrrhetinic-Acid-Based Derivatives.Molecules (Basel, Switzerland) · 2021Article
- Ursolic acid reduces hepatocellular apoptosis and alleviates alcohol-induced liver injury via irreversible inhibition of CASP3 in vivo.Acta pharmacologica Sinica · 2021Article
- Gasdermin E-derived caspase-3 inhibitors effectively protect mice from acute hepatic failure.Acta pharmacologica Sinica · 2021Article
- Caspases from scleractinian coral show unique regulatory features.The Journal of biological chemistry · 2020Article
- The Role of Caspase-2 in Regulating Cell Fate.Cells · 2020Review
- 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
- Design of a Human Rhinovirus-14 3C Protease-Inducible Caspase-3.Molecules (Basel, Switzerland) · 2019Article
- The CaspBase: a curated database for evolutionary biochemical studies of caspase functional divergence and ancestral sequence inference.Protein science : a publication of the Protein Society · 2018Article
- Modifications to a common phosphorylation network provide individualized control in caspases.The Journal of biological chemistry · 2018Article
- HOXC13 promotes proliferation of esophageal squamous cell carcinoma via repressing transcription of CASP3.Cancer science · 2018Article
- Ursolic Acid, a Natural Nutraceutical Agent, Targets Caspase3 and Alleviates Inflammation-Associated Downstream Signal Transduction.Molecular nutrition & food research · 2017Article
- 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
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
During maturation, procaspase-3 is cleaved at D175, which resides in a linker that connects the large and small subunits. The intersubunit linker also connects two active site loops that rearrange following cleavage and, in part, form the so-called loop bundle. As a result of chain cleavage, new hydrogen bonds and van der Waals contacts form among three active site loops. The new interactions are predicted to stabilize the active site. One unresolved issue is the extent to which the loop bundle residues also stabilize the procaspase active site. We examined the effects of replacing four loop bundle residues (E167, D169, E173, and Y203) on the biochemical and structural properties of the (pro)caspase. We show that replacing the residues affects the activity of the procaspase as well as the mature caspase, with D169A and E167A replacements having the largest effects. Replacement of D169 prevents caspase-3 autoactivation, and its cleavage at D175 no longer leads to an active enzyme. In addition, the E173A mutation, when coupled to a second mutation in the procaspase, D175A, may alter the substrate specificity of the procaspase. The mutations affected the active site environment as assessed by changes in fluorescence emission, accessibility to quencher, and cleavage by either trypsin or V8 proteases. High-resolution X-ray crystallographic structures of E167A, D173A, and Y203F caspases show that changes in the active site environment may be due to the increased flexibility of several residues in the N-terminus of the small subunit. Overall, the results show that these residues are important for stabilizing the procaspase active site as well as that of the mature caspase.
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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.