A5059973323- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Antimicrobial Peptides and Activities
- Cell Adhesion Molecules Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Bone Metabolism and Diseases
- Trypanosoma species research and implications
- Coccidia and coccidiosis research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Proteoglycans and glycosaminoglycans research
- Pulmonary Hypertension Research and Treatments
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Signaling Pathways in Disease
- Research on Leishmaniasis Studies
- Biochemical and Structural Characterization
- Trace Elements in Health
- Lysosomal Storage Disorders Research
- Bone health and treatments
- Bone and Dental Protein Studies
- S100 Proteins and Annexins
- Neonatal Respiratory Health Research
- Glycosylation and Glycoproteins Research
- Animal Nutrition and Physiology
- Calpain Protease Function and Regulation
- Oral microbiology and periodontitis research
Inserm
2014-2024
Centre d'Étude des Pathologies Respiratoires
2015-2024
Université de Tours
2014-2024
Thion Medical (France)
2022
Center for Economic and Policy Research
2020
Institut National de Recherche en Santé Publique
2005-2015
Icahn School of Medicine at Mount Sinai
2002-2013
Serine Proteases and Pathophysiology of the neurovascular Unit
2008-2012
Weatherford College
2009
Children's Hospital Agia Sophia
2009
The substrate specificities of papain-like cysteine proteases (clan CA, family C1) papain, bromelain, and human cathepsins L, V, K, S, F, B, five parasitic origin were studied using a completely diversified positional scanning synthetic combinatorial library. A bifunctional coumarin fluorophore was used that facilitated synthesis the library individual peptide substrates. has total 160,000 tetrapeptide sequences randomizing each P1, P2, P3, P4 positions with 20 amino acids. microtiter plate...
Voltage-gated sodium channels (Na(V)) are functionally expressed in highly metastatic cancer cells derived from nonexcitable epithelial tissues (breast, prostate, lung, and cervix). MDA-MB-231 breast express functional channel complexes, consisting of Na(V)1.5 associated auxiliary beta-subunits, that responsible for a sustained inward current at the membrane potential. Although these do not regulate cellular multiplication or migration, their inhibition by specific blocker tetrodotoxin...
"Click" protein: CuI-catalyzed cycloaddition of azides and terminal alkynes has been applied to the successive ligations three unprotected peptide fragments. Peptidomimetic triazole ligation (PTL, see scheme) as a new method for chemical production bioactive proteins is synthesis triazole-containing analogue 97 amino acid protein cystatin A. Detailed facts importance specialist readers are published "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They...
Human cysteine cathepsin S (catS) participates in distinct physiological and pathophysiological cellular processes is considered as a valuable therapeutic target autoimmune diseases, cancer, atherosclerosis, asthma. We evaluated the capacity of negatively charged glycosaminoglycans (heparin, heparan sulfate, chondroitin 4/6-sulfates, dermatan hyaluronic acid) to modulate activity catS. Chondroitin 4-sulfate (C4-S) impaired collagenolytic (type IV collagen) inhibited peptidase (Z-Phe-Arg-AMC)...
The aspartic protease cathepsin D, a poor prognostic indicator of breast cancer, is abundantly secreted as procathepsin D by human cancer cells and self-activates at low pH in vitro, giving rise to catalytically active D. Due lower extracellular tumor microenvironments compared normal tissues, may cleave pathophysiological substrates contributing progression. Here, we show yeast 2-hybrid degradomics analyses that cystatin C, the most potent natural inhibitor cysteine cathepsins, both binds...
Lung matrix homeostasis partly depends on the fine regulation of proteolytic activities. We examined expression human cysteine cathepsins (Cats) and their relative contribution to TGF-β1-induced fibroblast differentiation into myofibroblasts. Assays were conducted using both primary fibroblasts obtained from patients with idiopathic pulmonary fibrosis lung CCD-19Lu fibroblasts. Pharmacological inhibition genetic silencing Cat B diminished α-smooth muscle actin expression, delayed...
Abstract Pulmonary fibrosis is a progressive disease characterized by widespread accumulation of myofibroblasts and extracellular matrix components. Growing evidences support that cysteine cathepsins, embracing cathepsin B (CatB) affects TGF-β1-driven Smad pathway, along with their inhibitor cystatin C, participate in myofibrogenesis. Here we established curcumin, potent antifibrotic drug used traditional Asian medicine, impaired the expression both α-smooth muscle actin mature TGF-β1...
The primary specificity of papain-like cysteine proteases (family C1, clan CA) is determined by S2−P2 interactions. Despite the high amino acid sequence identities and structural similarities between cathepsins K L, only cathepsin capable cleaving interstitial collagens in their triple helical domains. To investigate this specificity, we have engineered S2 pocket human into a L-like subsite. Using combinatorial fluorogenic substrate libraries, P1−P4 variant, Tyr67Leu/Leu205Ala, was compared...
Lung cysteine cathepsins B, K, L, and S contribute to physiological pathological processes including degradation of antimicrobial peptides/proteins (AMPs) such as surfactant protein SP-A, lactoferrin, secretory leukocyte peptidase inhibitor, beta-defensins-2 -3. Substantial amounts uncleaved LL-37, a 37-mer cationic AMP, were observed in the sputum patients with cystic fibrosis (CF). Nevertheless LL-37 was degraded after prolonged incubation CF sputum, hydrolysis blocked by E-64, selective...
Cigarette smoking has marked effects on lung tissue, including induction of oxidative stress, inflammatory cell recruitment, and a protease/antiprotease imbalance. These contribute to tissue remodeling destruction resulting in loss function chronic obstructive pulmonary disease (COPD) patients. Cathepsin S (CatS) is cysteine protease that involved the remodeling/degradation connective basement membrane. Aberrant expression or activity CatS been implicated variety diseases, arthritis, cancer,...
The exchange of residues 67 and 205 the S2 pocket human cysteine cathepsins K L induces a permutation their substrate specificity toward fluorogenic peptide substrates. While cathepsin L-like (Tyr67Leu/Leu205Ala) mutant has marked preference for Phe, Leu67Tyr/Ala205Leu variant shows an effective K-like Leu Pro. A similar turnaround inhibition was observed by using specific inhibitors [1-(N-Benzyloxycarbonyl-leucyl)-5-(N-Boc-phenylalanyl-leucyl)carbohydrazide]...
Cathepsin S (catS), which is expressed in normal human keratinocytes and localized close to the dermal-epidermal junction (DEJ) degrades some of major basement membrane (BM) constituents. Among them, catS readily hydrolyzed a time dose dependent manner nidogen-1 (nid-1) nidogen-2, are key proteins BM structure. CatS preferentially cleaved nid-1 at both acid neutral pH. Hydrolysis was hampered murine ctss−/− spleen lysates pretreated with inhibitors other classes proteases. Nid-1 within its...
The limited availability of highly selective cathepsin substrates seriously impairs studies designed to monitor individual activities in biological samples. Among mammalian cysteine proteases, K has a unique preference for proline residue at P2, the primary determinant its substrate specificity. Interestingly, congopain from Trypanosoma congolense also accommodates S2 subsite. Analysis model showed that amino acids forming subsite are identical with those K, except Leu67 which is replaced by...
In the presence of oligomeric chondroitin 4-sulfate (C4-S), cathepsin K (catK) forms a specific complex that was shown to be source major collagenolytic activity in bone osteoclasts. C4-S multiple contacts with amino acid residues on backside catK molecule help facilitate formation. As L does not exhibit significant collagenase or absence C4-S, we substituted interacting those L. Variants revealed altered activities largest inhibitory effect by hexavariant M5. None variants showed reduction...