ArticleThe Journal of biological chemistry2012
Zinc-mediated allosteric inhibition of caspase-6.
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. An erratum has been issued. Cited by 54 papers.
What it found
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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
54 citing papers in PubMed, 84 citations in OpenAlex.
- Zinc-mediated structural and functional regulation of ERp44 and ERGIC-53 in protein quality control.Journal of biochemistry · 2026Review
- Engineering human RNase 7 with an eosinophil RNase segment reveals determinants of cytotoxic and antimicrobial activity.The Journal of biological chemistry · 2026Article
- The Intricate Role of Caspase-6 and Death Receptor-6 in Neurodegenerative Diseases.Cell biochemistry and biophysics · 2026Review
- APP-C31 pathology as a target in neurodegenerative diseases.Journal of biomedical science · 2026Review
- ZIP3 is essential for the encephalitogenic function of pTh17 cells by regulating intracellular zinc levels.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2026Article
- Development and Validation of a High-Throughput Screening Assay for the Legionella ADP-Ribosyl Transferase SdeA.Chembiochem : a European journal of chemical biology · 2025Article
- Evolution of the conformational ensemble and allosteric networks of apoptotic caspases in chordates.The Biochemical journal · 2025Article
- A histidine switch regulates pH-dependent filament formation by the caspase-9 CARD.bioRxiv : the preprint server for biology · 2025Article
- Interplay between PI3k/AKT signaling and caspase pathway in Alzheimer disease: mechanism and therapeutic implications.Inflammopharmacology · 2025Review
- Synthesis, cytotoxicity, apoptosis-inducing activity and molecular docking studies of novel isatin-podophyllotoxin hybrids.RSC advances · 2025Article
- An NMR sample preparation case study: Considerations for the self-destructive protease caspase-6.PloS one · 2025Article
- A role and mechanism for redox sensing by SENP1 in β-cell responses to high fat feeding.Nature communications · 2024Article
- Mesoporous zinc-polyphenol nanozyme for attenuating renal ischemia-reperfusion injury.Nanomedicine (London, England) · 2024Article
- The Implications of Insufficient Zinc on the Generation of Oxidative Stress Leading to Decreased Oocyte Quality.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- ZnACS omega · 2022Article
- Synthesis and biological activity, and molecular modelling studies of potent cytotoxic podophyllotoxin-naphthoquinone compounds.RSC advances · 2022Article
- Regulation of zinc-dependent enzymes by metal carrier proteins.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Review
- Aberrance of Zinc Metalloenzymes-Induced Human Diseases and Its Potential Mechanisms.Nutrients · 2021Review
- Transition metal cation inhibition of Mycobacterium tuberculosis esterase RV0045C.Protein science : a publication of the Protein Society · 2021Article
- Zinc: Multidimensional Effects on Living Organisms.Biomedicines · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Zinc and caspase-6 have independently been implicated in several neurodegenerative disorders. Depletion of zinc intracellularly leads to apoptosis by an unknown mechanism. Zinc inhibits cysteine proteases, including the apoptotic caspases, leading to the hypothesis that zinc-mediated inhibition of caspase-6 might contribute to its regulation in a neurodegenerative context. Using inductively coupled plasma optical emission spectroscopy, we observed that caspase-6 binds one zinc per monomer, under the same conditions where the zinc leads to complete loss of enzymatic activity. To understand the molecular details of zinc binding and inhibition, we performed an anomalous diffraction experiment above the zinc edge. The anomalous difference maps showed strong 5σ peaks, indicating the presence of one zinc/monomer bound at an exosite distal from the active site. Zinc was not observed bound to the active site. The zinc in the exosite was liganded by Lys-36, Glu-244, and His-287 with a water molecule serving as the fourth ligand, forming a distorted tetrahedral ligation sphere. This exosite appears to be unique to caspase-6, as the residues involved in zinc binding were not conserved across the caspase family. Our data suggest that binding of zinc at the exosite is the primary route of inhibition, potentially locking caspase-6 into the inactive helical conformation.
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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.