A5103123265- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Signaling Pathways in Disease
- HER2/EGFR in Cancer Research
- Rheumatoid Arthritis Research and Therapies
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Biochemical and Molecular Research
- Click Chemistry and Applications
- Immune Response and Inflammation
- Steroid Chemistry and Biochemistry
- Estrogen and related hormone effects
- Folate and B Vitamins Research
- Hormonal Regulation and Hypertension
- Porphyrin Metabolism and Disorders
- Toxin Mechanisms and Immunotoxins
- Computational Drug Discovery Methods
- Advanced Biosensing Techniques and Applications
- RNA modifications and cancer
- S100 Proteins and Annexins
- NF-κB Signaling Pathways
- Erythrocyte Function and Pathophysiology
- Advanced biosensing and bioanalysis techniques
- Research on Leishmaniasis Studies
BioZyme (United States)
2008-2019
Akita Industrial Technology Center
2010
Encana (Canada)
2008
Canadian Institutes of Health Research
2007
University of British Columbia
2007
Florida Atlantic University
2007
Astellas Pharma (South Korea)
2007
Victor (Japan)
2007
King's College London
2007
Research Triangle Park Foundation
1994-2004
Abstract CD163, a monocyte and macrophage-specific surface glycoprotein, which is increased by interleukin-10 glucocorticoids, scavenger receptor for hemoglobin/haptoglobin complexes. We report rapid highly reproducible rise in soluble CD163 the plasma of human volunteers given intravenous lipopolysaccharide (LPS). also show that LPS induces shedding from isolated monocytes, identifying monocytes macrophages as likely mechanism endotoxemia-associated vivo. Studies using inhibitor TAPI-0...
TNFα converting enzyme (TACE) processes precursor between Ala76 and Val77, yielding a correctly processed bioactive 17 kDa protein. Genetic evidence indicates that TACE may also be involved in the shedding of other ectodomains. Here we show native recombinant forms efficiently synthetic substrate corresponding to cleavage site only. For all substrates, conversion occurred only at high concentrations prolonged reaction times. Often, under those conditions was accompanied by nonspecific...
Hypomorphic ADAM17(ex/ex) mice showed defects in mucosal regeneration due to inefficient enhanced GFR shedding. ADAM17 is the main sheddase of interleukin-6 receptor (IL-6R) induce IL-6 trans-signaling. However, serum levels soluble murine IL-6R were not reduced mice, and was major IL-6R. Shedding by rescued chimeric proteins containing any extracellular domain but transmembrane intracellular human Apoptosis a physiological stimulus ADAM17-mediated shedding Even though apoptosis induced...
The tumor necrosis factor-α-converting enzyme (TACE) is a membrane-anchored zinc metalloprotease involved in precursor factor-α secretion. We designed series of constructs containing full-length human TACE and several truncate forms for overexpression insect cells. Here, we demonstrate that expressed cells inefficiently: only minor amounts this are converted from an inactive to the mature, functional form. Removal cytoplasmic transmembrane domains resulted efficient secretion active TACE....
ADAM10 is a disintegrin metalloproteinase that processes amyloid precursor protein and ErbB ligands involved in the shedding of many type I II single membrane-spanning proteins. Like tumor necrosis factor-alpha-converting enzyme (TACE or ADAM17), expressed as zymogen, removal prodomain results its activation. Here we report recombinant mouse prodomain, purified from Escherichia coli, potent competitive inhibitor human catalytic/disintegrin domain, with K(i) 48 nM. Moreover, selective it only...
The interconversion of L-lysine and L-3,6-diamino-hexanoate (L-beta-lysine) catalyzed by lysine 2,3-aminomutase is known to be stimulated added S-adenosylmethionine (Chirpich, T. P., Zappia, V., Costilow, R. N., Barker, H. A. (1970) J. Biol. Chem. 245, 1778-1789). In this paper we show that enzyme activated S-[2,8,5'-3H]adenosylmethionine catalyzes the conversion equilibrium mixture L-beta-lysine with incorporation high levels tritium into both isomers. in isomers reflect constant for their...
The neural cell adhesion molecule "close homologue of L1," termed CHL1, has functional importance in the nervous system. CHL1 is expressed as a transmembrane protein 185 kDa, and ectodomain shedding releases soluble fragments relevant for its physiological function. Here we describe that ADAM8, member family metalloprotease disintegrins cleaves CHL1-Fc fusion vitro at two sites corresponding to release extracellular domain fibronectin (FN) domains II (125 kDa) V (165 kDa), inhibited by...
Matrix metalloproteinases (MMPs) and A Disintegrin Metalloproteinases (ADAMs) are two related protease families that play key roles in matrix remodeling growth factor ligand shedding. Directly ascertaining the proteolytic activities of particular MMPs ADAMs physiological environments a non-invasive, real-time, multiplex manner remains challenge. This work describes Proteolytic Activity Analysis (PrAMA), an integrated experimental measurement mathematical analysis framework for simultaneously...
The substrate specificity of human collagenase 3 (MMP-13), a member the matrix metalloproteinase family, is investigated using phage-displayed random hexapeptide library containing 2 × 10<sup>8</sup> independent recombinants. A total 35 phage clones that express peptide sequence can be hydrolyzed by recombinant catalytic domain are identified. translated DNA these reveals highly conserved putative P1, P2, P3 and P1′, P2′, P3′ subsites substrates. Kinetic analysis synthetic substrates made...
The low affinity IgE receptor, FcepsilonRII (CD23), is both a positive and negative regulator of synthesis. proteinase activity that converts the membrane-bound form CD23 into soluble species (sCD23) an important function may be therapeutic target for control allergy inflammation. We have characterized catalytic ADAM (a disintegrin metalloproteinase) 10 toward human CD23. found ADAM10 efficiently catalyzes cleavage peptides derived from two distinct sites in backbone. Tissue inhibitors...
The conversion of L-lysine to L-beta-lysine is catalyzed by lysine 2,3-aminomutase. reaction involves the interchange 2-amino group with a hydrogen at carbon 3. As such formally analogous adenosylcobalamin-dependent rearrangements. However, enzyme does not contain and activated this coenzyme. Instead it contains iron pyridoxal phosphate S-adenosylmethionine. Earlier experiments implicated adenosyl-C-5' S-adenosylmethionine in transfer mechanism, apparently role similar or that adenosyl...
Tumor necrosis factor α (TNF-α) is a potent cytokine in neurodegenerative disorders, but its precise role particular brain disorders ambiguous. In motor neuron (MN) disease of the mouse, exemplified by model wobbler (WR), TNF-α causes upregulation metalloprotease-disintegrin ADAM8 (A8) affected regions, spinal cord, and brainstem. The functional A8 during MN degeneration CNS was investigated crossing WR with A8-deficient mice: severely aggravated neuropathology observed for compared +/−...
Prodomains of A disintegrin and metalloproteinase (ADAM) metallopeptidases can act as highly specific intra- intermolecular inhibitors ADAM catalytic activity. The mouse ADAM9 prodomain (proA9; amino acids 24-204), expressed characterized from Escherichia coli, is a competitive inhibitor human catalytic/disintegrin domain with an overall inhibition constant 280 ± 34 nM high specificity toward ADAM9. In SY5Y neuroblastoma cells overexpressing amyloid precursor protein, proA9 treatment reduces...
// Hinrich P. Hansen 1 , Ahmad Trad 2 Maria Dams Paola Zigrino 3 Marcia Moss 4 Maximilian Tator Gisela Schön Patricia C Grenzi Daniel Bachurski Bruno Aquino 5 Horst Dürkop 6 Katrin S Reiners Michael von Bergwelt-Baildon Hallek Joachim Grötzinger Andreas Engert Adriana F Paes Leme Elke Pogge Strandmann Department of Internal Medicine I, University Cologne, Germany Biochemistry, Kiel, Dermatology, BioZyme Inc., Apex, North Carolina, USA Brazilian Biosciences National Laboratory,...