Cysteine Proteinase Inhibitors
Amino Acid Sequence
Molecular Sequence Data
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Electrophoresis, Polyacrylamide Gel
Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S. (1/1976)The lysosomal cysteine proteases cathepsins S and L play crucial roles in the degradation of the invariant chain during maturation of MHC class II molecules and antigen processing. The p41 form of the invariant chain includes a fragment which specifically inhibits cathepsin L but not S. The crystal structure of the p41 fragment, a homologue of the thyroglobulin type-1 domains, has been determined at 2.0 A resolution in complex with cathepsin L. The structure of the p41 fragment demonstrates a novel fold, consisting of two subdomains, each stabilized by disulfide bridges. The first subdomain is an alpha-helix-beta-strand arrangement, whereas the second subdomain has a predominantly beta-strand arrangement. The wedge shape and three-loop arrangement of the p41 fragment bound to the active site cleft of cathepsin L are reminiscent of the inhibitory edge of cystatins, thus demonstrating the first example of convergent evolution observed in cysteine protease inhibitors. However, the different fold of the p41 fragment results in additional contacts with the top of the R-domain of the enzymes, which defines the specificity-determining S2 and S1' substrate-binding sites. This enables inhibitors based on the thyroglobulin type-1 domain fold, in contrast to the rather non-selective cystatins, to exhibit specificity for their target enzymes. (+info)
Bile duct epithelial cells exposed to alpha-naphthylisothiocyanate produce a factor that causes neutrophil-dependent hepatocellular injury in vitro. (2/1976)The acute hepatotoxicity induced by alpha-naphthylisothiocyanate (ANIT) in rats is manifested as neutrophil-dependent necrosis of bile duct epithelial cells (BDECs) and hepatic parenchymal cells. This hepatotoxicity mirrors that of drug-induced cholangiolitic hepatitis in humans. Since BDECs are primary targets of ANIT-induced toxicity, we hypothesized that after exposure to ANIT, BDECs produce a factor(s) that causes neutrophil chemotaxis and neutrophil-dependent hepatocellular injury. To test this hypothesis BDECs were isolated from male Sprague Dawley rats and incubated with ANIT (6.25, 12.5, 25, or 50 microM) or vehicle for 24 h. The conditioned medium (CM) was collected and placed in the bottom chamber of a two-chambered chemotaxis system, while isolated neutrophils were placed in the top chamber. Chemotaxis was indicated by neutrophil migration through a membrane to the bottom chamber. CM from BDECs exposed to each concentration of ANIT was chemotactic, whereas CM from vehicle-treated BDECs was not. ANIT alone caused a modest degree of chemotaxis at 50 microM. The conditioned media were added to isolated hepatocytes or to hepatocyte-neutrophil cocultures and incubated for 24 h. Hepatocyte toxicity was indicated by alanine aminotransferase release into the culture medium. CM from vehicle-treated BDECs did not cause hepatocyte killing in either hepatocyte-neutrophil cocultures or hepatocyte cultures. In contrast, the addition of CM from ANIT-treated BDECs (CM-BDEC-A) to hepatocyte-neutrophil cocultures resulted in hepatocyte killing. The same CM was not cytotoxic to hepatocyte cultures devoid of neutrophils. The hepatocyte killing could not be explained by residual ANIT in the CM, which was below the limit of detection (< or = 0.5 microM). The addition of antiproteases afforded protection against neutrophil-dependent hepatocellular injury induced by CM-BDEC-A. These results indicate that ANIT causes BDECs to release a factor(s) that attracts neutrophils and stimulates them to injure hepatocytes in vitro. (+info)
Crystal structure of wild-type human procathepsin K. (3/1976)Cathepsin K is a lysosomal cysteine protease belonging to the papain superfamily. It has been implicated as a major mediator of osteoclastic bone resorption. Wild-type human procathepsin K has been crystallized in a glycosylated and a deglycosylated form. The latter crystals diffract better, to 3.2 A resolution, and contain four molecules in the asymmetric unit. The structure was solved by molecular replacement and refined to an R-factor of 0.194. The N-terminal fragment of the proregion forms a globular domain while the C-terminal segment is extended and shows substantial flexibility. The proregion interacts with the enzyme along the substrate binding groove and along the proregion binding loop (residues Ser138-Asn156). It binds to the active site in the opposite direction to that of natural substrates. The overall binding mode of the proregion to cathepsin K is similar to that observed in cathepsin L, caricain, and cathepsin B, but there are local differences that likely contribute to the specificity of these proregions for their cognate enzymes. The main observed difference is in the position of the short helix alpha3p (67p-75p), which occupies the S' subsites. As in the other proenzymes, the proregion utilizes the S2 subsite for anchoring by placing a leucine side chain there, according to the specificity of cathepsin K toward its substrate. (+info)
The intracellular serpin proteinase inhibitor 6 is expressed in monocytes and granulocytes and is a potent inhibitor of the azurophilic granule protease, cathepsin G. (4/1976)The monocyte and granulocyte azurophilic granule proteinases elastase, proteinase 3, and cathepsin G are implicated in acute and chronic diseases thought to result from an imbalance between the secreted proteinase(s) and circulating serpins such as alpha1-proteinase inhibitor and alpha1-antichymotrypsin. We show here that the intracellular serpin, proteinase inhibitor 6 (PI-6), is present in monocytes, granulocytes, and myelomonocytic cell lines. In extracts from these cells, PI-6 bound an endogenous membrane-associated serine proteinase to form an sodium dodecyl sulfate (SDS)-stable complex. Using antibodies to urokinase, elastase, proteinase 3, or cathepsin G, we demonstrated that the complex contains cathepsin G. Native cathepsin G and recombinant PI-6 formed an SDS-stable complex in vitro similar in size to that observed in the extracts. Further kinetic analysis demonstrated that cathepsin G and PI-6 rapidly form a tight 1:1 complex (ka = 6.8 +/- 0.2 x 10(6) mol/L-1s-1 at 17 degrees C; Ki = 9.2 +/- 0.04 x 10(-10) mol/L). We propose that PI-6 complements alpha1-proteinase inhibitor and alpha1-antichymotrypsin (which control extracellular proteolysis) by neutralizing cathepsin G that leaks into the cytoplasm of monocytes or granulocytes during biosynthesis or phagocytosis. Control of intracellular cathepsin G may be particularly important, because it has recently been shown to activate the proapoptotic proteinase, caspase-7. (+info)
Cathepsin S required for normal MHC class II peptide loading and germinal center development. (5/1976)Major histocompatibility complex (MHC) class II molecules acquire antigenic peptides after degradation of the invariant chain (Ii), an MHC class II-associated protein that otherwise blocks peptide binding. Antigen-presenting cells of mice that lack the protease cathepsin S fail to process Ii beyond a 10 kDa fragment, resulting in delayed peptide loading and accumulation of cell surface MHC class II/10 kDa Ii complexes. Although cathepsin S-deficient mice have normal numbers of B and T cells and normal IgE responses, they show markedly impaired antibody class switching to IgG2a and IgG3. These results indicate cathepsin S is a major Ii-processing enzyme in splenocytes and dendritic cells. Its role in humoral immunity critically depends on how antigens access the immune system. (+info)
Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice. (6/1976)Cathepsins have been implicated in the degradation of proteins destined for the MHC class II processing pathway and in the proteolytic removal of invariant chain (Ii), a critical regulator of MHC class II function. Mice lacking the lysosomal cysteine proteinase cathepsin S (catS) demonstrated a profound inhibition of Ii degradation in professional APC in vivo. A marked variation in the generation of MHC class II-bound Ii fragments and presentation of exogenous proteins was observed between B cells, dendritic cells, and macrophages lacking catS. CatS-deficient mice showed diminished susceptibility to collagen-induced arthritis, suggesting a potential therapeutic target for regulation of immune responsiveness. (+info)
Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis. (7/1976)Cathepsin K, a lysosomal cysteine protease critical for bone remodeling by osteoclasts, was recently identified as the deficient enzyme causing pycnodysostosis, an autosomal recessive osteosclerotic skeletal dysplasia. To investigate the nature of molecular lesions causing this disease, mutations in the cathepsin K gene from eight families were determined, identifying seven novel mutations (K52X, G79E, Q190X, Y212C, A277E, A277V, and R312G). Expression of the first pro region missense mutation in a cysteine protease, G79E, in Pichia pastoris resulted in an unstable precursor protein, consistent with misfolding of the proenzyme. Expression of five mature region missense defects revealed that G146R, A277E, A277V, and R312G precursors were unstable, and no mature proteins or protease activity were detected. The Y212C precursor was activated to its mature form in a manner similar to that of the wild-type cathepsin K. The mature Y212C enzyme retained its dipeptide substrate specificity and gelatinolytic activity, but it had markedly decreased activity toward type I collagen and a cathepsin K-specific tripeptide substrate, indicating that it was unable to bind collagen triple helix. These studies demonstrated the molecular heterogeneity of mutations causing pycnodysostosis, indicated that pro region conformation directs proper folding of the proenzyme, and suggested that the cathepsin K active site contains a critical collagen-binding domain. (+info)
Vaccination with cathepsin L proteinases and with leucine aminopeptidase induces high levels of protection against fascioliasis in sheep. (8/1976)The potential of different parasite proteinases for use as vaccine candidates against fascioliasis in sheep was studied by vaccinating animals with the cathepsin L proteinases CL1 and CL2 and with leucine aminopeptidase (LAP) purified from adult flukes. In the first trial, sheep were immunized with CL1 or CL2 and the mean protection levels obtained were 33 and 34%, respectively. Furthermore, a significant reduction in egg output was observed in sheep vaccinated either with CL1 (71%) or with CL2 (81%). The second trial was performed to determine the protective potential of the two cathepsin L proteinases assayed together, as well as in combination with LAP, and of LAP alone. The combination of CL1 and CL2 induced higher levels of protection (60%) than those produced when these enzymes were administered separately. Those sheep that received the cocktail vaccine including CL1, CL2, and LAP were significantly protected (78%) against metacercarial challenge, but vaccination with LAP alone elicited the highest level of protection (89%). All vaccine preparations induced high immunoglobulin G titers which were boosted after the challenge infection, but no correlations between antibody titers and worm burdens were found. However, the sera of those animals vaccinated with LAP contained LAP-neutralizing antibodies. Reduced liver damage, as assessed by the level of the liver enzyme gamma-glutamyl transferase, was observed in the groups vaccinated with CL1, CL2, and LAP or with LAP alone. (+info)
The main symptoms of PLD include:
* Skin manifestations: The disease typically presents with thickened, scaly skin on the palms and soles, as well as on the fingers and toes. The skin may also be darkly pigmented and have a characteristic "café-au-lait" appearance.
* Nervous system abnormalities: PLD can cause neurological symptoms such as intellectual disability, seizures, and difficulty with coordination and balance.
* Eye problems: The disease may also cause vision loss due to cataracts or other eye defects.
PLD is usually diagnosed through a combination of clinical evaluation, skin biopsy, and genetic testing. There is no cure for the disease, but treatment options are available to manage the symptoms. These may include:
* Medications: To control seizures and other neurological symptoms, medications such as anticonvulsants and anti-epileptic drugs may be prescribed.
* Surgery: In some cases, surgery may be necessary to remove affected skin or to correct eye defects.
* Physical therapy: To help improve coordination and balance, physical therapy may be recommended.
The prognosis for PLD is generally poor, with many individuals experiencing significant developmental delays and intellectual disability. However, with appropriate management and supportive care, some individuals with the disease may lead relatively normal lives.
What is the definition of Cathepsins? | Dictionary.net
Pro-cathepsin D, Prosaposin, and Progranulin: Lysosomal Networks in Parkinsonism - PubMed
Cathepsin G | Inflammatory Bowel Disease | Arotec Diagnostics
Cathepsin L regulates pathogenic CD4 T cells in experimental autoimmune encephalomyelitis - List Labs
Destabilizing role of cathepsin S in murine atherosclerotic plaques<...
cathepsin - NIH Director's Blog
Cathepsin S Cleavage of Protease-Activated Receptor-2 on Endothelial Cells Promotes Microvascular Diabetes Complications -...
cathepsin B | NIH Intramural Research Program
Sequence and expression of the cDNA for MEP (major excreted protein), a transformation-regulated secreted cathepsin.<...
Lysosomal lipid alterations caused by glucocerebrosidase deficiency promote lysosomal dysfunction, chaperone-mediated-autophagy...
Cathepsin L, Human Liver | 219402
Weighted gene coexpression network analysis reveals negative regulation of hypertrophic cardiomyopathy by carboxylesterase 1...
Cathepsin G 293T Transfected Lysate - (positive control)
Cathepsin G FRET substrate [5-FAM]/[6-TAMRA] - CRB Discovery
Recombinant Mouse Cathepsin S/CTSS Protein (His Tag) - Fagus Antibody Services
1tzs.1 | SWISS-MODEL Template Library
6-Shogaol has anti-amyloidogenic activity and ameliorates Alzheimer's disease via CysLT1R-mediated inhibition of cathepsin B
Impairment of microglial responses to facial nerve axotomy in cathepsin S-deficient mice<...
JACC Podcast: Cathepsin-S Levels and Survival among Patients with Non-ST Elevation Acute Coronary Syndromes
AbMiner - Antibody Detail | Genomics and Pharmacology Facility
Cathepsin-Cleavable BIM BH3 Peptide Amphiphiles Are Potent Inducers of Cellular Apoptosis | Blood | American Society of...
MedlinePlus: Genetic Conditions: D
Rotablation of Intensely Calcified Remaining Primary Stenosis and also Aortic Device Valvuloplasty Below ECMO Cardiopulmonary...
DailyMed - VEMLIDY- tenofovir alafenamide tablet
Autoantibodies as Diagnostic Markers and Mediator of Joint Inflammation in Arthritis
Expansion of cytochrome P450 and cathepsin genes in the generalist herbivore brown marmorated stink bug | BMC Genomics | Full...
Background Cathepsin K, a cysteine protease predominantly expressed in osteoclasts, is - Discovery and optimization of potent...
MBS8245107 | hsa-mir-504 Real-Time RT-PCR Detection and cel-mir-39-3p Calibration Kit
Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling (Journal Article) | DOE...
- Previously we reported that IL-17-producing CD4 T cells (Th17) were increased in mice lacking the protease inhibitor SerpinB1 and several SerpinB1-inhibitable cysteine cathepsins were induced in the Th17 cells, most prominently cathepsin L (CtsL). (listlabs.com)
- Substrate peptide for Cathepsin G, a serine protease belonging to the chymotrypsin superfamily which acts as a physiologic regulator of platelet activation and thrombus formation. (crbdiscovery.com)
- Cathepsin G can cleave protease activated receptor-4 (PAR4) and is a potential target for novel anti-thrombotic therapies. (crbdiscovery.com)
- Cathepsin S (CS) is a lysosomal/endosomal cysteine protease especially expressed in cells of a mononuclear lineage including microglia. (elsevierpure.com)
- Interestingly, cathepsin B, a typical lysosomal cysteine protease, was markedly expressed on the axotomized side in CS-/- but not in wild-type microglia. (elsevierpure.com)
- Moreover, we clarified the relationship between CysLT1R and cathepsin B, a cysteine protease. (nih.gov)
- Background Cathepsin K, a cysteine protease predominantly expressed in osteoclasts, is a significant drug focus on for the treating osteoporosis. (monossabios.com)
- solid course="kwd-title" Keywords: lung airway, cathepsin K, TGF-1, extracellular matrix, protease inhibitors Background Cathepsin K (CatK) is certainly a lysosomal cysteine protease with powerful collagenolytic and elastolytic actions. (monossabios.com)
- In this research, the interactions between specific flavonols and the 2019-nCoV receptor binding domain (RBD), transmembrane protease, serine 2 (TMPRSS2), and cathepsins (CatB and CatL) were analyzed. (afsu.edu.tr)
- Cathepsin G, a 225 amino acid residue protein with an 18 residue signal peptide and a 2 residue activation peptide at the N-terminus, is a ubiquitous enzyme secreted by neutrophils. (arodia.com)
- 2003) Bactericidal/permeability-increasing protein and cathepsin G are the major antigenic targets of antineutrophil cytoplasmic autoantibodies in systemic sclerosis. (arodia.com)
- Sequence and expression of the cDNA for MEP (major excreted protein), a transformation-regulated secreted cathepsin. (elsevier.com)
- Dive into the research topics of 'Sequence and expression of the cDNA for MEP (major excreted protein), a transformation-regulated secreted cathepsin. (elsevier.com)
- The most potent of the lysosomal proteinases, having a higher activity than cathepsins B and H in the degradation of a variety of physiological protein substrates. (emdmillipore.com)
- 2018). Caspase-4 activation by a bacterial surface protein is mediated by cathepsin G in human gingival fibroblasts Cell Death Differ . (crbdiscovery.com)
- It's been reported the fact that secretion of development factors such as for example TGF-1 and changed appearance of matrix degrading enzymes such as for example cathepsins  donate to structural adjustments in the ECM. (monossabios.com)
- The cathepsin B enzymes from NEJ flukes have recently been demonstrated to be crucial to invasion and migration by the parasite. (edu.au)
- Here we characterize one of the cathepsin B enzymes (recombinant FhcatB1) from NEJ flukes. (edu.au)
- FhcatB1 has biochemical properties distinct from mammalian cathepsin B enzymes, with an atypical preference for Ile over Leu or Arg residues at the P2 substrate position and an inability to act as an exopeptidase. (edu.au)
- Crystalline silica also was reported to cause adverse renal effects in test animals and to inhibit some enzymes (e.g., cathepsin B) while inducing others (CYP1A1). (nih.gov)
- Cathepsin G is a member of the hematopoietic serine proteinase super family along with elastase and proteinase 3. (arodia.com)
- We found that the expression of carboxylesterase 1 (CES1) and cathepsin C (CTSC) was downregulated in HCM tissues and negatively correlated with Maxi LVWT. (bvsalud.org)
- 1997) Anti-neutrophil cytoplasmic antibody (ANCA) in malaria is directed against cathepsin G. Clin. (arodia.com)
- SDS-PAGE - Cathepsin G 293T Transfected Lysate (ab94086) All lanes : Anti-Cathepsin G antibody (ab89593) at 1/500 dilution Lane 1 : Cathepsin G 293T Transfected Lysate - (positive control) (ab94086) Lane 2 : 293T non-transfected lysate Lysates/proteins at 25 µg per lane. (studylib.net)
- TGF-1 demonstrated a competent substrate of cathepsin K and TGF-1 proteins articles in lung was elevated with a potent cathepsin inhibitor. (monossabios.com)
- Our results indicate that 6-shogaol is a CysLT1R/cathepsin B inhibitor and is a novel potential therapeutic agent for the treatment of various neurodegenerative diseases, including AD. (nih.gov)
- 1996) Cathepsin G in gingival tissue and crevicular fluid in adult periodontosis. (arodia.com)
- Cathepsin G also has antimicrobial activity and is involved in chemotaxis, apoptosis, the immune response and inflammation and hydrolysis of extracellular matrix proteins. (crbdiscovery.com)
- Product datasheet Cathepsin G 293T Transfected Lysate - (positive control) ab94086 2 Images Overview Product name Cathepsin G 293T Transfected Lysate - (positive control) General notes ab94086 is a 293T cell transfected lysate in which Human Cathepsin G has been transiently over-expressed using a pCMV-Cathepsin G plasmid. (studylib.net)
- The convenience of TGF-1 to cathepsin K-mediated degradation was identified em in vitro PU-H71 /em and lung fibroblast proliferations in wild-type and cathepsin K-deficient cells had been evaluated. (monossabios.com)
- Strong homology of MEP with human cathepsin L suggests that MEP is the mouse analogue of cathepsin L. Amino acid sequencing of the N-terminus of the secreted form of MEP indicates that, during secretion, the polypeptide is cleaved between amino acids 17 and 18. (elsevier.com)
- Cathepsin L, Human Liver, CAS 60616-82-2, is a native, the most potent of all the lysosomal proteinases. (emdmillipore.com)
- Compared with the abundant cathepsins B, L and H, cathepsin S shows a restricted tissue distribution, with highest levels in spleen, heart, and lung. (fagusantibodies.com)
- In subsequent RT-PCR experiments, both P450 and cathepsin genes exhibited tissue-specific or distinct expression patterns which supported their principal roles of detoxification and/or digestion in a particular tissue. (biomedcentral.com)
- Cathepsin S is a lysosomal enzyme that belongs to the papain family of cysteine proteases. (fagusantibodies.com)
- Recombinant Mouse Cathepsin S is produced by our Mammalian expression system and the target gene encoding Val18-Ile340 is expressed with a 6His tag at the C-terminus. (fagusantibodies.com)
- We first confirmed that CysLT1R and cathepsin B are upregulated by Aβ (1-42) and that CysLT1R activation induces cathepsin B. In contrast, we found that 6-shogaol-mediated inhibition of CysLT1R downregulates cathepsin B in both in vitro and in vivo models. (nih.gov)
- 2013). Cathepsin G-Dependent Modulation of Platelet Thrombus Formation In Vivo by Blood Neutrophils. (crbdiscovery.com)
- Lung homogenates of wild-type and cathepsin K-deficient mice had been used to judge their material of collagen, glycosaminoglycans, and TGF-1. (monossabios.com)
- Outcomes Lung airway cathepsin K manifestation in wild-type mice continued to be continuous between 1 and six months of age as well as the airway integrity was managed. (monossabios.com)
- Hai, PH , Doh-Ura, K & Nakanishi, H 2007, ' Impairment of microglial responses to facial nerve axotomy in cathepsin S-deficient mice ', Journal of Neuroscience Research , vol. 85, no. 10, pp. 2196-2206. (elsevierpure.com)
- Furthermore, we found that 6-shogaol-mediated inhibition of CysLT1R/cathepsin B reduces Aβ deposition in the brain and ameliorates behavioral deficits in APPSw/PS1-dE9 Tg mice. (nih.gov)
- Inflammasome activation was confirmed using inhibitors of cathepsin B and Caspase-1. (cdc.gov)
- Independent of its proteinase activity, cathepsin G is a significant broad spectrum anti-microbial agent. (arodia.com)
- There is published data that ANCA associated antibodies against cathepsin G are found in ulcerative colitis and crohn's disease. (arodia.com)
- 2000) Anti-cathepsin G antibodies in the sera of patients with ulcerative colitis. (arodia.com)
- Our analysis into P450 and cathepsin genes in H. halys offers new insights into potential mechanisms for understanding generalist herbivory and adaptation success in invasive habitats. (biomedcentral.com)
- The expected use of healing cathepsin K inhibitors must take potential adjustments in individual lungs under consideration. (monossabios.com)
- Bottom line This study shows that airway advancement is partly governed by cathepsin K which its appearance plays a part in the maintenance of the airway structural integrity. (monossabios.com)
- Weighted gene coexpression network analysis reveals negative regulation of hypertrophic cardiomyopathy by carboxylesterase 1 and cathepsin C. (bvsalud.org)
- Following a comprehensive transcriptome analysis, H. halys had an expanded suite of cytochrome P450 and cathepsin-L genes compared to other insects. (biomedcentral.com)
- My work on the cathepsins, the secreted cathepsins, just gradually became less and less important. (nih.gov)