Last update 01 Nov 2024

CTSZ

Last update 01 Nov 2024

Basic Info

Synonyms

carboxypeptidase LB, cathepsin B2, cathepsin IV

+ [9]

Introduction

Exhibits carboxy-monopeptidase as well as carboxy-dipeptidase activity (PubMed:10504234). Capable of producing kinin potentiating peptides (By similarity).

Drugs associated with CTSZ

WO2024136397

Patent Mining

Target

CTSZ

Mechanism-

Active Org.

Nbios, Inc. [+1]

Originator Org.

Kookmin University Industry-Academic Cooperation [+1]

Active Indication

Neoplasms [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CTSZ

100 Translational Medicine associated with CTSZ

0 Patents (Medical) associated with CTSZ

274

Literatures (Medical) associated with CTSZ

01 Dec 2024·Cellular and Molecular Life Sciences

Cellular depletion of major cathepsin proteases reveals their concerted activities for lysosomal proteolysis

Article

Author: Bleibaum, Florian ; Saftig, Paul ; Spengler, Katharina ; Gallwitz, Lisa ; Müller, Stephan ; Damme, Markus ; Zöphel, Frederic ; Winter, Dominic ; Schweizer, Michaela ; Voss, Matthias ; Lichtenthaler, Stefan

AbstractProteins delivered by endocytosis or autophagy to lysosomes are degraded by exo- and endoproteases. In humans 15 lysosomal cathepsins (CTS) act as important physiological regulators. The cysteine proteases CTSB and CTSL and the aspartic protease CTSD are the most abundant and functional important lysosomal proteinases. Whereas their general functions in proteolysis in the lysosome, their individual substrate, cleavage specificity, and their possible sequential action on substrate proteins have been previously studied, their functional redundancy is still poorly understood. To address a possible common role of highly expressed and functional important CTS proteases, we generated CTSB-, CTSD-, CTSL-, and CTSBDL-triple deficient (KO) human neuroblastoma-derived SH-SY5Y cells and CTSB-, CTSD-, CTSL-, CTSZ and CTSBDLZ-quadruple deficient (KO) HeLa cells. These cells with a combined cathepsin deficiency exhibited enlarged lysosomes and accumulated lipofuscin-like storage material. The lack of the three (SH-SY5Y) or four (HeLa) major CTSs caused an impaired autophagic flux and reduced degradation of endocytosed albumin. Proteome analyses of parental and CTS-depleted cells revealed an enrichment of cleaved peptides, lysosome/autophagy-associated proteins, and potentially endocytosed membrane proteins like the amyloid precursor protein (APP), which can be subject to endocytic degradation. Amino- and carboxyterminal APP fragments accumulated in the multiple CTS-deficient cells, suggesting that multiple CTS-mediated cleavage events regularly process APP. In summary, our analyses support the idea that different lysosomal cathepsins act in concert, have at least partially and functionally redundant substrates, regulate protein degradation in autophagy, and control cellular proteostasis, as exemplified by their involvement in the degradation of APP fragments.

07 Oct 2024·G3: Genes, Genomes, Genetics

T and Z, partial seed coat patterning genes in common bean, provide insight into the structure and protein interactions of a plant MBW complex

Article

Author: Osorno, Juan M ; Lee, Rian ; McClean, Phillip E ; Colbert, Christopher L ; Roy, Jayanta ; Osborne, Caroline ; Miklas, Phillip N

AbstractFlavonoids are secondary metabolites associated with plant seed coat and flower color. These compounds provide health benefits to humans as anti-inflammatory and antioxidant compounds. The expression of the late biosynthetic genes in the flavonoid pathway is controlled by a ternary MBW protein complex consisting of interfacing MYB, beta-helix–loop–helix (bHLH), and WD40 Repeat (WDR) proteins. P, the master regulator gene of the flavonoid expression in common bean (Phaseolus vulgaris L.), was recently determined to encode a bHLH protein. The T and Z genes control the distribution of color in bean seeds and flowers and have historically been considered regulators of the flavonoid gene expression. T and Z candidates were identified using reverse genetics based on genetic mapping, phylogenetic analysis, and mutant analysis. Domain and AlphaFold2 structure analyses determined that T encodes a seven-bladed β-propeller WDR protein, while Z encodes a R2R3 MYB protein. Deletions and SNPs in T and Z mutants, respectively, altered the 3D structure of these proteins. Modeling of the Z MYB/P bHLH/T WDR MBW complex identified interfacing sequence domains and motifs in all three genes that are conserved in dicots. One Z MYB motif is a possible beta-molecular recognition feature (β-MoRF) that only appears in a structured state when Z MYB is modeled as a component of a MBW complex. Complexes containing mutant T and Z proteins changed the interaction of members of the complex in ways that would alter their role in regulating the expression of genes in the flavonoid pathway.

01 Sep 2024·International Journal of Biological Macromolecules

Fabrication of cysteine-modified antibodies with Fc-specific conjugation for covalent and oriented immobilization of native antibodies

Article

Author: Yang, Hong-Ming ; Wang, Feng-Shan ; Xu, Chong-Mei ; Pan, Zheng-Xuan ; Zhang, Yu-Min ; Du, Yue ; Tang, Jin-Bao

Covalent and oriented immobilization of antibodies (Abs) can substantially improve the sensitivity and stability of solid-phase immunoassays. By modifying the natural Abs with functional groups that provide unique handles for further conjugation, Abs could be immobilized onto the solid matrices with uniform orientation. Herein, an effective approach for Fc-specific modification of Abs was developed for the oriented and covalent immobilization of Abs. Twelve photoreactive Z-domain variants, incorporated with a photoactivable probe (p-benzoyl-L-phenylalanine, Bpa) at different positions and carrying a C-terminal Cys-tag (i.e. Z_Bpa-Cys variants), were individually constructed and produced in Escherichia coli and tested for photo-cross-linking to various IgGs. The different Z_Bpa-Cys variants demonstrated large differences in photo-conjugation efficiency for the tested IgGs. The conjugation efficiencies of ^17thZ_Bpa-Cys ranged from 90 % to nearly 100 % for rabbit IgG and mouse IgG_2a, IgG_2b and IgG₃. Other variants, including ^5thZ_Bpa-Cys, ^18thZ_Bpa-Cys, ^32thZ_Bpa-Cys, and ^35thZ_Bpa-Cys, also displayed conjugation efficiencies of 61 %-83 % for mouse IgG₁, IgG_2a and IgG₃. Subsequently, the photo-modified Abs, namely IgG-Cys conjugates, were covalently immobilized onto a maleimide group-functionalized solid-phase carrier on the basis of the reaction of sulfhydryl and maleimide. Thus, a generic platform for the controlled and oriented immobilization of Abs was developed, and the efficacy and potential of the proposed approach for sensitive immunoassays was demonstrated by detecting human α-fetoprotein.

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CTSZ

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