The Role of Gly-4 of Human Cystatin A (Stefin A) in the Binding of Target Proteinases. Characterization by Kinetic and Equilibrium Methods of the Interactions of Cystatin A Gly-4 Mutants with Papain, Cathepsin B, and Cathepsin L†

Biochemistry ◽  
1998 ◽  
Vol 37 (20) ◽  
pp. 7551-7560 ◽  
Author(s):  
Sergio Estrada ◽  
Maria Nycander ◽  
Nikki J. Hill ◽  
C. Jeremy Craven ◽  
Jonathan P. Waltho ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Cathepsin L ◽  
Stefin A ◽  
Cystatin A ◽  
Human Cystatin

scholarly journals Effects of microbial proteinase inhibitors on the degradation of endogenous and internalized proteins by rat yolk sacs

1981 ◽  
Vol 196 (1) ◽  
pp. 41-48 ◽  
Author(s):  
S E Knowles ◽  
F J Ballard ◽  
G Livesey ◽  
K E Williams
Keyword(s):  
Bovine Serum Albumin ◽  
Cathepsin B ◽  
Proteinase Inhibitors ◽  
Cathepsin L ◽  
Minor Role ◽  
Protein Breakdown ◽  
Inhibitory Effects ◽  
Endogenous Protein ◽  
A Minor

1. The effects of leupeptin and other microbial proteinase inhibitors were measured in rat yolk sacs on the uptake and degradation of formaldehyde-denatured 125I-labelled bovine serum albumin as well as on the degradation of 3H-labelled endogenous protein. 2. Leupeptin, at concentrations between 1 and 100 micrograms/ml, inhibits the degradation of added albumin without affecting pinocytic uptake. Accordingly large amounts of undegraded albumin accumulate within the tissue. 3. Removal of leupeptin produces a rapid recovery of the capacity to degrade albumin. 4. Endogenous protein degradation is rapidly inhibited by leupeptin, but to a far lesser extent than the breakdown of albumin. However, the inhibition is only slightly reversed on removal of leupeptin. 5. Degradation of both albumin and endogenous protein in intact yolk sacs is inhibited by the microbial proteinase inhibitors in the order: leupeptin greater than antipain greater than chymostatin; elastatinal, pepstatin and bestatin are ineffective. 6. Similar results are found when albumin is incubated in yolk-sac homogenates at pH 4 with the inhibitors. 7. The marked inhibitory effects of leupeptin, antipain and chymostatin suggest that cathepsin B and possibly cathepsin L participate in the degradation of 125I-labelled albumin in yolk sacs. By comparison, the smaller inhibitory effects of the proteinase inhibitors on endogenous protein breakdown imply a minor role of lysosomal cathepsins in this process.

scholarly journals Role of Endosomal Cathepsins in Entry Mediated by the Ebola Virus Glycoprotein

2006 ◽  
Vol 80 (8) ◽  
pp. 4174-4178 ◽  
Author(s):  
Kathryn Schornberg ◽  
Shutoku Matsuyama ◽  
Kirsten Kabsch ◽  
Sue Delos ◽  
Amy Bouton ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Ebola Virus ◽  
Cathepsin L ◽  
Low Ph ◽  
Virus Glycoprotein ◽  
Infection Treatment ◽  
Chemical Inhibitors ◽  
Ph Dependent ◽  
Interfering Rna

ABSTRACT Using chemical inhibitors and small interfering RNA (siRNA), we have confirmed roles for cathepsin B (CatB) and cathepsin L (CatL) in Ebola virus glycoprotein (GP)-mediated infection. Treatment of Ebola virus GP pseudovirions with CatB and CatL converts GP1 from a 130-kDa to a 19-kDa species. Virus with 19-kDa GP1 displays significantly enhanced infection and is largely resistant to the effects of the CatB inhibitor and siRNA, but it still requires a low-pH-dependent endosomal/lysosomal function. These and other results support a model in which CatB and CatL prime GP by generating a 19-kDa intermediate that can be acted upon by an as yet unidentified endosomal/lysosomal enzyme to trigger fusion.

Solution structure of a human cystatin A variant, cystatin A2-98 M65L by NMR spectroscopy. A possible role of the interactions between the N- and C-termini to maintain the inhibitory active form of cystatin A

Biochemistry ◽  
1995 ◽  
Vol 34 (45) ◽  
pp. 14637-14648 ◽  
Author(s):  
Shin-ichi Tate ◽  
Toshio Ushioda ◽  
Naoko Utsunomiya-Tate ◽  
Kazunori Shibuya ◽  
Yukihito Ohyama ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Solution Structure ◽  
Active Form ◽  
Cystatin A ◽  
Human Cystatin

scholarly journals Cathepsin B and D deficiency in the mouse pancreas induces impaired autophagy and chronic pancreatitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hideaki Iwama ◽  
Sally Mehanna ◽  
Mai Imasaka ◽  
Shinsuke Hashidume ◽  
Hiroshi Nishiura ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Cathepsin B ◽  
Gene Knockout ◽  
Cathepsin L ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Double Knockout ◽  
Lysosomal Proteases ◽  
Autophagic Activity

AbstractThe major lysosomal proteases, Cathepsin B (CTSB), Cathepsin D (CTSD) and Cathepsin L (CTSL), are implicated in autophagic activity. To investigate the role of each cathepsin in the exocrine pancreas, we generated mice in which the pancreas was specifically deficient in Ctsb, Ctsd and Ctsl. Each of these gene knockout (KO) and Ctsb;Ctsl and Ctsd;Ctsl double-knockout (DKO) mice were almost normal. However, we found cytoplasmic degeneration in the pancreatic acinar cells of Ctsb;Ctsd DKO mice, similar to autophagy related 5 (Atg5) KO mice. LC3 and p62 (autophagy markers) showed remarkable accumulation and the numbers of autophagosomes and autolysosomes were increased in the pancreatic acinar cells of Ctsb;Ctsd DKO mice. Moreover, these Ctsb;Ctsd DKO mice also developed chronic pancreatitis (CP). Thus, we conclude that both Ctsb and Ctsd deficiency caused impaired autophagy in the pancreatic acinar cells, and induced CP in mice.

scholarly journals Sero-prevalence of toxoplasmosis and Role of Cathepsin L-like and Cathepsin B-like Genes as Risk Factors for Abnormal Pregnancy Outcome

2020 ◽  
Vol 30 (4) ◽  
pp. 43
Author(s):  
Noor Meran Omer ◽  
Hadi M. A. Alsakee
Keyword(s):  
Risk Factors ◽  
Pregnancy Outcome ◽  
Cathepsin B ◽  
Cathepsin L ◽  
Reproductive Age ◽  
Host Cells ◽  
Cross Sectional ◽  
Abnormal Pregnancy ◽  
Pcr Targeting

Background and objectives: Toxoplasma gondii (T. gondii) is a ubiquitous apicomplexan parasite. As an obligate intracellular parasite, T. gondii must invade host cells to survive and replicate. Five cathepsin proteases are encoded in the genome of T. gondii, cathepsin L like protein, cathepsin B like protein, and three cathepsin C like proteins. The present study was aimed to investigate the prevalence of toxoplasmosis among women in Erbil, and to study the role of cathepsin B and cathepsin L genes in the pathogenesis of toxoplasmosis as well as their role as risk factors for abnormal pregnancy outcome. Methods: This is a cross sectional study was carried out in Erbil from October 2018 to March 2019.  A total of 230 women at their reproductive age and who attended Maternity Teaching Hospital and Nazdar Bamarni primary Health Center were enrolled. Anti- toxoplasma IgG and IgM antibodies were detected by cobas 6000. Toxoplasma cathepsin B and cathepsin L – like genes were selected to be targets in PCR. Results: Anti-toxoplasma IgG and IgM were seropositive in 105 (45.7%) and 18 (7.8%) women, respectively. Of those women who were seropositive for toxoplasmosis, only 15(6.5%) of them were carrying both anti-toxoplasma IgG and IgM. No significant association of toxoplasmosis and educational level, socioeconomic level, age, history of abortion, abnormal baby birth weight were observed. PCR targeting cathepsin L was more sensitive to be used in the diagnosis of toxoplasmosis. Conclusion: Sero-prevalence of toxoplasmosis is relatively high in Erbil and cathepsin L gene is an efficient target for PCR and could be used as risk factor for abnormal pregnancy outcome.

scholarly journals Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Miao-Miao Zhao ◽  
Wei-Li Yang ◽  
Fang-Yuan Yang ◽  
Li Zhang ◽  
Wei-Jin Huang ◽  
...  
Keyword(s):  
Drug Development ◽  
Cathepsin L ◽  
Human Cells ◽  
New Drugs ◽  
Disease Course ◽  
Promising Target ◽  
First Time

AbstractTo discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

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