A5077831601- Immunodeficiency and Autoimmune Disorders
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Urticaria and Related Conditions
- Systemic Lupus Erythematosus Research
- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Physics and Engineering Research Articles
- Viral Infections and Vectors
- Inflammatory Myopathies and Dermatomyositis
- Biomedical and Chemical Research
- Peripheral Neuropathies and Disorders
- Autoimmune Bullous Skin Diseases
- Reproductive Biology and Fertility
- Mosquito-borne diseases and control
- Medical and Health Sciences Research
- Chronic Lymphocytic Leukemia Research
- Blood disorders and treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Platelet Disorders and Treatments
- Atherosclerosis and Cardiovascular Diseases
- Immune Cell Function and Interaction
- Sperm and Testicular Function
- Adrenal Hormones and Disorders
- Vasculitis and related conditions
Johannes Gutenberg University Mainz
2013-2023
Euroimmun Medizinische Labordiagnostika (Germany)
2017-2019
American Association for Clinical Chemistry
2019
Zentrum für Labormedizin
2019
Siemens Healthcare (Germany)
2018
Matrix Biology Institute
2015
University of Münster
1999-2004
Hahnemann University Hospital
2000
Heidelberg University
1990-1999
Max Planck Institute of Biochemistry
1995
Astacins are secreted and membrane-bound metalloproteases with clear associations to many important pathological physiological processes. Yet only a few substrates described their biological roles enigmatic. Moreover, the lack of knowledge astacin cleavage site specificities hampers assay drug development. Using PICS (proteomic identification protease specificity) TAILS (terminal amine isotopic labeling substrates) degradomics approaches >3000 sites were proteomically identified for five...
Meprin is a zinc endopeptidase of the astacin family, which expressed as membrane-bound or secreted protein in mammalian epithelial cells, intestinal leucocytes and certain cancer cells. There are two types meprin subunits, alpha beta, form disulphide-bonded homo- hetero-oligomers. Here we report on cleavage matrix proteins by hmeprin (human meprin) beta homo-oligomers, interactions these enzymes with inhibitors. Despite their completely different specificities, both able to hydrolyse...
Ectodomain shedding at the cell surface is a major mechanism to regulate extracellular and circulatory concentration or activities of signaling proteins plasma membrane. Human meprin β 145-kDa disulfide-linked homodimeric multidomain type-I membrane metallopeptidase that sheds membrane-bound cytokines growth factors, thereby contributing inflammatory diseases, angiogenesis, tumor progression. In addition, it cleaves amyloid precursor protein (APP) β-secretase site, giving rise amyloidogenic...
Astacin, a zinc‐endopeptidase from the crayfish Astacus astacus L., represents structurally distinct group of metalloproteinases termed ‘astacin family’. This protein family includes oligomeric membrane‐bound proteins with zinc proteinase domains found in rodent kidneys (meprins A and B) human small intestine ( N ‐benzoyl‐ l ‐tyrosyl‐4‐aminobenzoate hydrolase). Another branch this comprises morphogenetically active proteins, which induce bone formation (human morphogenetic 1), or play...
Proteolysis is regulated by inactive (latent) zymogens, with a prosegment preventing access of substrates to the active-site cleft enzyme. How latency maintained often depends on catalytic mechanism protease. For example, in several families metzincin metallopeptidases, "cysteine switch" involves conserved motif cysteine residue that coordinates zinc ion. Another family metzincins, astacins, do not possess switch, so other means. We have solved high resolution crystal structure proastacin...
Meprin α and β, zinc metalloproteinases, play significant roles in inflammation, including inflammatory bowel disease (IBD), possibly by activating cytokines, like interleukin 1β, 18, or tumor growth factor α. Although a number of potential activators for meprins are known, no endogenous inhibitors have been identified. In this work, we analyzed the inhibitory human plasma identified bovine fetuin-A as an meprin inhibitor with K(i) (inhibition constant) 4.2 × 10(-5) M 1.1 10(-6) β. This...
Abstract Vertebrate fetuins are multi-domain plasma-proteins of the cystatin-superfamily. Human fetuin-A is also known as AHSG, α 2 -Heremans-Schmid-glycoprotein. Gene-knockout in mice identified essential for calcified-matrix-metabolism and bone-mineralization. Fetuin-B deficient mice, on other hand, female infertile due to zona pellucida ‘hardening’ caused by metalloproteinase ovastacin unfertilized oocytes. In wildtype fetuin-B inhibits activity thus maintaining oocytes fertilizable. Here...
Meprins are zinc-endopeptidases of the astacin family, which expressed as membrane-bound or secreted forms in renal and intestinal brush-border membranes mouse, rat man. There two types meprin subunits, α β, form disulfide-bonded homo- heterodimers; further oligomerization is mediated by non-covalent interactions. Both subunits translated proenzymes that have to be activated removal an N-terminal propeptide. In gut, most probable activator trypsin. addition, plasmin has been shown activate...
The catalytic zinc ion of astacin, a prototypical metalloproteinase from crayfish, has been substituted by Co(II), Cu(II), Hg(II), and Ni(I1) in order to probe the role metal for both catalysis structure.Compared Zn(I1)-astacin, Co(I1)-and Cu(I1)-astacin display enzymatic activities about 140 37%, respectively, while Ni(I1)-and Hg(I1)-astacin are almost inactive.The electron paramagnetic resonance spectrum is typical 5-fold coordinated copper(II), its intense absorption maxima at 446 325 n m...
Bone morphogenetic protein-1 (BMP-1) and the tolloid-like metalloproteinases control several aspects of embryonic development tissue repair. Unlike other proteinases whose activities are regulated mainly by endogenous inhibitors, regulation BMP-1/tolloid-like relies mostly on proteins that stimulate activity. Among these, procollagen C-proteinase enhancers (PCPEs) markedly increase proteinase activity fibrillar procollagens, in a substrate-specific manner. Here, we performed detailed...