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)

Lens neutral proteinase is thought to exhibit primarily endopeptidase activity. We have identified a synthetic endopeptidase substrate which is hydrolyzed by the bovine lens neutral proteinase preparation. Among 11 fluoro- and chromogenic endopeptidase substrates, only carbobenzoxy-glycylglycyl-L-leucyl-p-nitroanilide is effectively hydrolyzed. The activity hydrolyzing this substrate co-elutes with neutral proteinase activity upon gel filtration and specifically attacks the leucyl-p-nitroaniline bond. Optimal hydrolysis of the synthetic substrate is at neutral pH and high temperature (53 degrees C), analogous to the alpha-crystallin protein substrate obtained from lens. The rate of hydrolysis of the synthetic substrate increased proportionally with temperature between 20 and 60 degrees C, in contrast to alpha-crystallin. The rate of hydrolysis was linear for at least 1 h at 37 degrees C and there was no evidence of enzyme activation at high temperature.
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PMID:A synthetic endopeptidase substrate hydrolyzed by the bovine lens neutral proteinase preparation. 637 46

Eukaryotic cells contain a major intracellular proteolytic activity known as the proteasome. The proteasome is a strongly conserved cylindrical structure of high molecular weight (650 kDa, approximately 20 S) and demonstrates multiple endopeptidase activities. The general structural, biochemical and genetic features of the proteasome are conserved from archaebacteria through yeast to humans. This structure fulfills an essential role by functioning as the proteolytic core of a 26 S multienzyme complex responsible for the energy-dependent degradation of ubiquitinated proteins. The bulk of intracellular proteolysis appears to be through the ubiquitin-dependent pathway. Incorporation of the proteasome into the 26 S multienzyme complex appears to confer both a specificity for ubiquitinated proteins as well as a means to tightly regulate proteolytic activity. Thus, one function of the proteasome is required for the degradation of either abnormal or certain regulatory proteins by the ubiquitin pathway. Proteasome subunits appear to be encoded by a related gene family as defined by extensive sequence similarities. The gene products are confined to either of two general classes: alpha-type which appear to be structural and beta-type which may be catalytic. Genes encoding at least two proteasome subunits map to the Major Histocompatibility Complex. Accumulating evidence points to the proteasome (or a specialized form) participating in the cytosolic degradation of these viral proteins upon cellular infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of the proteasome in cellular protein degradation. 800 15

Intracellular proteins are degraded by the proteasome, and resulting peptides surviving cytoplasmic peptidase activity can be presented by MHC class I molecules. Here, we show that intracellular aminopeptidases degrade peptides within seconds, almost irrespectively of amino acid sequence. N- but not C-terminal extension increases the half-life of peptides until they are 15 amino acids long. Beyond 15 amino acids, peptides are exclusively trimmed by the peptidase TPPII, which displays both exo- and endopeptidase activity. Surprisingly, most proteasomal degradation products are handled by TPPII before presentation by MHC class I molecules. We define three distinct proteolytic activities during antigen processing in vivo. Proteasome-generated peptides relevant for antigen presentation are mostly 15 amino acids or longer. These require TPPII activity for further trimming before becoming substrates for other peptidases and MHC class I. The heterogeneous pool of aminopeptidases will process TPPII products into MHC class I peptides and beyond.
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PMID:A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation. 1508 65

Membrane metallo-endopeptidase (MME), also known as neutral endopeptidase 24.11 (EC 3.4.24.11), is involved in the metabolism of natriuretic peptides that play a key role in modulating cardiac structure and function. Common genetic variation in MME has not been addressed by resequencing the gene using DNA from different ethnic populations. We set out to identify and functionally characterize common genetic variation in MME in three ethnic groups. DNA samples from 96 European-American, 96 African-American, and 96 Han Chinese-American healthy subjects were used to resequence MME. Ninety polymorphisms, 65 novel, were identified, including 8 nonsynonymous single nucleotide polymorphisms (nsSNPs). Expression constructs for the nsSNPs were created and COS-1 cells were transfected with constructs for wild type (WT) and variant allozymes. Recombinant proteins were analyzed by quantitative Western blot analysis and by a one-step fluorometric assay. A significant reduction in enzyme activity (21% of WT) and immunoreactive protein (29% of WT) for the Val73 variant allozyme was observed. Proteasome-mediated degradation and autophagy participated in the degradation of this variant allozyme. The chaperone proteins, BiP and GRP94, were upregulated after transfection with Val73 MME, suggesting protein misfolding, compatible with conclusions based on the MME X-ray crystal structure. Multiple novel polymorphisms of MME were identified in three ethnic groups. The Val73 variant allozyme displayed a significant decrease in MME protein quantity and activity, with degradation mediated by both proteasome and autophagy pathways. This polymorphism could have a significant effect on the metabolism of natriuretic peptides.
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PMID:Natriuretic peptide pharmacogenetics: membrane metallo-endopeptidase (MME): common gene sequence variation, functional characterization and degradation. 2069 64