Protease Substrate Identification Using N-terminomics

2019 ◽  
Vol 14 (11) ◽  
pp. 2361-2371 ◽  
Author(s):  
Shu Yue Luo ◽  
Luam Ellen Araya ◽  
Olivier Julien
Keyword(s):  
Substrate Identification ◽  
Protease Substrate

scholarly journals Quantitative proteomics in plant protease substrate identification

2017 ◽  
Vol 218 (3) ◽  
pp. 936-943 ◽  
Author(s):  
Fatih Demir ◽  
Stefan Niedermaier ◽  
Joji Grace Villamor ◽  
Pitter Florian Huesgen
Keyword(s):  
Quantitative Proteomics ◽  
Plant Protease ◽  
Substrate Identification ◽  
Protease Substrate

Phenotype of the herpes simplex virus type 1 protease substrate ICP35 mutant virus.

1994 ◽  
Vol 68 (9) ◽  
pp. 5384-5394 ◽  
Author(s):  
L Matusick-Kumar ◽  
W Hurlburt ◽  
S P Weinheimer ◽  
W W Newcomb ◽  
J C Brown ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Mutant Virus ◽  
Protease Substrate ◽  
Simplex Virus

scholarly journals An automated protocol for modelling peptide substrates to proteases

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Rodrigo Ochoa ◽  
Mikhail Magnitov ◽  
Roman A. Laskowski ◽  
Pilar Cossio ◽  
Janet M. Thornton
Keyword(s):  
Substrate Recognition ◽  
Accessible Surface Area ◽  
Conformational Sampling ◽  
Structural Determinants ◽  
Peptide Substrates ◽  
The Family ◽  
Protease Substrate ◽  
Peptide Complexes ◽  
Accessible Surface ◽  
Automated Protocol

Abstract Background Proteases are key drivers in many biological processes, in part due to their specificity towards their substrates. However, depending on the family and molecular function, they can also display substrate promiscuity which can also be essential. Databases compiling specificity matrices derived from experimental assays have provided valuable insights into protease substrate recognition. Despite this, there are still gaps in our knowledge of the structural determinants. Here, we compile a set of protease crystal structures with bound peptide-like ligands to create a protocol for modelling substrates bound to protease structures, and for studying observables associated to the binding recognition. Results As an application, we modelled a subset of protease–peptide complexes for which experimental cleavage data are available to compare with informational entropies obtained from protease–specificity matrices. The modelled complexes were subjected to conformational sampling using the Backrub method in Rosetta, and multiple observables from the simulations were calculated and compared per peptide position. We found that some of the calculated structural observables, such as the relative accessible surface area and the interaction energy, can help characterize a protease’s substrate recognition, giving insights for the potential prediction of novel substrates by combining additional approaches. Conclusion Overall, our approach provides a repository of protease structures with annotated data, and an open source computational protocol to reproduce the modelling and dynamic analysis of the protease–peptide complexes.

scholarly journals A cytokine receptor-masked IL2 prodrug selectively activates tumor-infiltrating lymphocytes for potent antitumor therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eric J. Hsu ◽  
Xuezhi Cao ◽  
Benjamin Moon ◽  
Joonbeom Bae ◽  
Zhichen Sun ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Interleukin 2 ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Checkpoint Blockade ◽  
Targeting Therapy ◽  
Protease Substrate ◽  
Reduced Toxicity ◽  
Infiltrating Lymphocytes ◽  
Receptor Beta

AbstractAs a potent lymphocyte activator, interleukin-2 (IL-2) is an FDA-approved treatment for multiple metastatic cancers. However, its clinical use is limited by short half-life, low potency, and severe in vivo toxicity. Current IL-2 engineering strategies exhibit evidence of peripheral cytotoxicity. Here, we address these issues by engineering an IL-2 prodrug (ProIL2). We mask the activity of a CD8 T cell-preferential IL-2 mutein/Fc fusion protein with IL2 receptor beta linked to a tumor-associated protease substrate. ProIL2 restores activity after cleavage by tumor-associated enzymes, and preferentially activates inside tumors, where it expands antigen-specific CD8 T cells. This significantly reduces IL-2 toxicity and mortality without compromising antitumor efficacy. ProIL2 also overcomes resistance of cancers to immune checkpoint blockade. Lastly, neoadjuvant ProIL2 treatment can eliminate metastatic cancer through an abscopal effect. Taken together, our approach presents an effective tumor targeting therapy with reduced toxicity.

scholarly journals A novel theranostic activity-based probe targeting kallikrein 7 for diagnosis and treatment of skin diseases

2021 ◽  
Author(s):  
Evangelos Bisyris ◽  
Eleni Zingkou ◽  
Golfo G Kordopati ◽  
Minos-Timotheos Matsoukas ◽  
Plato A. Magriotis ◽  
...  
Keyword(s):  
In Silico ◽  
Skin Diseases ◽  
Diagnosis And Treatment ◽  
Protease Substrate

We applied a new in silico approach for fishing protease-substrate motifs to design a kallirein 7 (KLK7)-specific phosphonate activity-based probe (ABP) to quantify the active KLK7 in situ. Epidermal application...

Profiling serine protease substrate specificity with solution phase fluorogenic peptide microarrays

PROTEOMICS ◽  
2005 ◽  
Vol 5 (5) ◽  
pp. 1292-1298 ◽  
Author(s):  
Dhaval N. Gosalia ◽  
Cleo M. Salisbury ◽  
Dustin J. Maly ◽  
Jonathan A. Ellman ◽  
Scott L. Diamond
Keyword(s):  
Substrate Specificity ◽  
Serine Protease ◽  
Solution Phase ◽  
Peptide Microarrays ◽  
Protease Substrate ◽  
Fluorogenic Peptide

Simultaneous orthogonal bipole mapping compared to conventional electrode configurations and impact on ablation strategies: results from a real world observational study

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
L Fiedler ◽  
F Roithinger ◽  
I Roca ◽  
F Lorgat ◽  
A Roux ◽  
...  
Keyword(s):  
Catheter Ablation ◽  
Observational Study ◽  
Real World ◽  
Low Voltage ◽  
High Density ◽  
Electrode Configuration ◽  
Density Mapping ◽  
Substrate Identification ◽  
Myocardial Substrate ◽  
Vt Ablation

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Abbott Background 3D mapping systems are pivotal to identify low voltage areas and to define ablation strategies. In this context, high-density multipolar mapping catheters with varying electrode configurations are used for accurate myocardial substrate definition. High density mapping using a grid shaped catheter allows for use of simultaneous analysis of adjacent orthogonal bipolar signals that may assist in more accurate substrate characterization and ablation strategy decisions. Purpose This was a prospective, multicenter observational study to characterize the utility of electroanatomical mapping with a high density grid-style mapping catheter (HD Grid) in subjects undergoing catheter ablation for persistent atrial fibrillation (PersAF) or ventricular tachycardia (VT) in real-world clinical settings. Methods Mapping was performed with the HD Grid catheter to generate high-density maps of cardiac chambers in order to assess the potential influence of the simultaneous orthogonal bipole configuration on PersAF and VT ablation strategies. Differences in substrate identification between simultaneous orthogonal bipole configuration and standard along-the-spline electrode configuration, and potential effects on ablation strategies were investigated. Results During the study period (January 2019 through April 2020), 367 subjects underwent catheter ablation for PersAF (N = 333, average age 64.1yr, 75% male) or VT (N = 34, average age = 64.3yr, 85.3% male). In total, 494 maps were generated to treat patients undergoing PersAF ablation and 57 to treat patients undergoing VT ablation. Compared to standard along-the-spline configuration, mapping with the simultaneous orthogonal bipole configuration showed differences in 57.8% (178/308) of maps generated, with the greatest difference noticed in surface area of low voltage (62.9%) and location of low voltage (55.6%). In comparisons performed live during the procedure (n = 50), simultaneous orthogonal bipole configuration assisted in identification of ablation targets in 70.0% of cases, changing the ablation strategy compared to that identified with along-the-spline configuration in 34.3%. In comparisons performed retrospectively after the procedure (n = 258), the ablation strategy identified with simultaneous orthogonal bipole configuration differed from along-the-spline configuration in 21.7% of maps. Even compared to a higher-density electrode configuration using all-bipoles rather than along-the-spline bipoles, simultaneous orthogonal bipole configuration identified differences in 57.1% of maps. Conclusion The HD grid catheter combined with simultaneous orthogonal bipole configuration can define myocardial substrate more accurately compared to standard along-the-spline configuration. The difference in substrate identification has potential impact on ablation strategy. Further clinical trials are needed to elucidate the role of orthogonal bipole configuration mapping and improved ablation success rates.

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