Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substantial protection against the economically important parasitic nematode Haemonchus contortus has been achieved by immunizing sheep with a glycoprotein fraction isolated from the intestinal membranes of the worm (H-gal-GP). Previous studies showed that one of the major components of H-gal-GP is a family of at least 4 zinc metalloendopeptidases, designated MEPs 1-4. This paper describes aspects of the molecular architecture of this protease family, including the proteomic analysis of the MEP fraction of the H-gal-GP complex. These enzymes belong to the M13 zinc metalloendopeptidase family (EC 3.4.24.11), also known as neutral endopeptidases or neprilysins. The sequences of MEPs 1 and 3 suggested a typical Type II integral membrane protein structure, whilst MEPs 2 and 4 had putative cleavable signal peptides, typical of secreted proteins. Proteomic analysis of H-gal-GP indicated that the extracellular domain of all 4 MEPs had been cleaved close to the transmembrane region/signal peptide with additional cleavage sites mid-way along the polypeptide. MEP3 was present as a homo-dimer in H-gal-GP, whereas MEP1 or MEP2 formed hetero-dimers with MEP4. It was found that expression of MEP3 was confined to developing 4th-stage larvae and to adult worms, the stages of Haemonchus which feed on blood. MEP-like activity was detected in the H-gal-GP complex over a broad pH range (5-9). Since all 4 MEPs must share a similar microenvironment in the complex, this suggests that each might have a different substrate specificity.
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PMID:Molecular characterization of a family of metalloendopeptidases from the intestinal brush border of Haemonchus contortus. 1674 Jan 78

Neprilysin is a zinc metalloendopeptidase with relatively broad substrate specificity. The enzyme is localized to the plasma membrane of cells where it can function to degrade extracellular peptides. Structural studies show that neprilysin preferentially cleaves peptides on the amino side of hydrophobic amino acids. Neprilysin has been implicated in the catabolism of amyloid beta peptides in the brain and as such has received considerable attention, particularly as a therapeutic target for Alzheimer's disease. An inverse relationship between neprilysin levels and amyloid beta peptide levels and between neprilysin levels and amyloid plaque formation has been observed in human brain. Neprilysin levels decline with aging in the temporal and frontal cortex possibly contributing to higher amyloid beta peptide levels. A number of studies have shown that increasing neprilysin levels in the brain leads to a decrease in brain amyloid beta peptide levels. Most recently a potential relationship between amyloid beta peptide synthesis from the amyloid precursor protein and neprilysin activity has been proposed.
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PMID:Neprilysin and amyloid beta peptide degradation. 1839 7

Our previous data showed that neprilysin (NEP), a zinc metalloendopeptidase, which can degrade amyloid-beta peptide (Abeta) whose central nerve system accumulation is the primary cause of Alzheimer's disease (AD), responds to estrogen in the brain. Recently, it has been shown that the transcription of the neprilysin gene can be up regulated by progesterone, androgens, and glucocorticoids through two androgen response elements within the NEP gene--an androgen response region (ARR) and an androgen response element (ARE). Through a yeast report gene system, we now find that the ARR but not the ARE respond to estrogen. However, androgen could efficiently enhance the expression of the report gene mainly through ARE. Our results indicate that the decrease of NEP, caused by the decline of estrogen or androgen with aging, may be an important factor leading to Abeta accumulation and AD.
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PMID:Estrogen regulation of the neprilysin gene through a hormone-responsive element. 1912 46


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