ArticleACS chemical biology2016
Reprogramming Caspase-7 Specificity by Regio-Specific Mutations and Selection Provides Alternate Solutions for Substrate Recognition.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed.
- Data-driven protease engineering by DNA-recording and epistasis-aware machine learning.Nature communications · 2025Article
- General Theory of Specific Binding: Insights from a Genetic-Mechano-Chemical Protein Model.Molecular biology and evolution · 2022Article
- Making the cut with protease engineering.Cell chemical biology · 2022Review
- Non-Apoptotic Caspase Activity Preferentially Targets a Novel Consensus Sequence Associated With Cytoskeletal Proteins in the Developing Auditory Brainstem.Frontiers in cell and developmental biology · 2022Article
- Deorphanizing Caspase-3 and Caspase-9 Substrates In and Out of Apoptosis with Deep Substrate Profiling.ACS chemical biology · 2021Article
- Evolution of the folding landscape of effector caspases.The Journal of biological chemistry · 2021Article
- Caspase-9 Activation of Procaspase-3 but Not Procaspase-6 Is Based on the Local Context of Cleavage Site Motifs and on Sequence.Biochemistry · 2021Article
- Exogenous Introduction of Initiator and Executioner Caspases Results in Different Apoptotic Outcomes.JACS Au · 2021Article
- N-Terminomics Strategies for Protease Substrates Profiling.Molecules (Basel, Switzerland) · 2021Review
- Rare CASP6N73T variant associated with hippocampal volume exhibits decreased proteolytic activity, synaptic transmission defect, and neurodegeneration.Scientific reports · 2021Article
- Phage-assisted evolution of botulinum neurotoxin proteases with reprogrammed specificity.Science (New York, N.Y.) · 2021Article
- Caspase-Activated Oligonucleotide Probe.Bioconjugate chemistry · 2020Article
- Sequential Glycosylation of Proteins with Substrate-SpecificACS central science · 2020Article
- Resurrection of ancestral effector caspases identifies novel networks for evolution of substrate specificity.The Biochemical journal · 2019Review
- Caspase-7 uses RNA to enhance proteolysis of poly(ADP-ribose) polymerase 1 and other RNA-binding proteins.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A Nanopore Approach for Analysis of Caspase-7 Activity in Cell Lysates.Biophysical journal · 2019Article
- Tri-arginine exosite patch of caspase-6 recruits substrates for hydrolysis.The Journal of biological chemistry · 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
- Multiple Mechanisms of Zinc-Mediated Inhibition for the Apoptotic Caspases-3, -6, -7, and -8.ACS 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
The ability to routinely engineer protease specificity can allow us to better understand and modulate their biology for expanded therapeutic and industrial applications. Here, we report a new approach based on a caged green fluorescent protein (CA-GFP) reporter that allows for flow-cytometry-based selection in bacteria or other cell types enabling selection of intracellular protease specificity, regardless of the compositional complexity of the protease. Here, we apply this approach to introduce the specificity of caspase-6 into caspase-7, an intracellular cysteine protease important in cellular remodeling and cell death. We found that substitution of substrate-contacting residues from caspase-6 into caspase-7 was ineffective, yielding an inactive enzyme, whereas saturation mutagenesis at these positions and selection by directed evolution produced active caspases. The process produced a number of nonobvious mutations that enabled conversion of the caspase-7 specificity to match caspase-6. The structures of the evolved-specificity caspase-7 (esCasp-7) revealed alternate binding modes for the substrate, including reorganization of an active site loop. Profiling the entire human proteome of esCasp-7 by N-terminomics demonstrated that the global specificity toward natural protein substrates is remarkably similar to that of caspase-6. Because the esCasp-7 maintained the core of caspase-7, we were able to identify a caspase-6 substrate, lamin C, that we predict relies on an exosite for substrate recognition. These reprogrammed proteases may be the first tool built with the express intent of distinguishing exosite dependent or independent substrates. This approach to specificity reprogramming should also be generalizable across a wide range of proteases.
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.