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

Proteolytic removal of the pre-segment from growing nascent chains of pre-human placental lactogen (hPL) occurred during in vitro translation of placental mRNA if crude membranes derived from ascites lysates, dog pancreas, or rat liver rough endoplasmic reticulum were added to the translation mixtures. The cotranslational proteolytic event was inhibited by the peptide protease inhibitor, chymostatin, but not by leupeptin, antipain, or elastatinal. The proteases involved in cleavage were solubilized with detergent and converted completed pre-hPL to hPL (post-translational processing). Direct assay of the solubilized membranes, with synthetic fluorogenic aminocoumarin peptide substrates, revealed no significant tryptic or elastase-like activity, but activity against a chymotrypsin substrate [(succinyl-Ala-Ala-Phe)-7-amino-4-methyl-coumarin] was found. This activity was dependent upon both an endopeptidase and an aminopeptidase. Although bestatin inhibited the aminopeptidase activity, it had no effect on the endopeptidase or on post-translational cleavage. Although this endopeptidase cleaved on the COOH side of an alanine residue, it was not inhibited by elastatinal. However, it was inhibited by high levels of chymostatin and by some serine protease inhibitors.
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PMID:Characterization of an endopeptidase involved in pre-protein processing. 29 60

We have isolated heparan sulfate proteoglycans (HSPGs) from cloned rat microvascular endothelial cells using a combination of ion-exchange chromatography, affinity fractionation with antithrombin III (AT III), and gel filtration in denaturing solvents. The anticoagulantly active heparan sulfate proteoglycans (HSPGact) which bind tightly to AT III bear mainly anticoagulantly active heparan sulfate (HSact) whereas the anticoagulantly inactive heparan sulfate proteoglycans (HSPGinact) possess mainly anticoagulantly inactive heparan sulfate (HSinact). HSact and HSinact were also isolated by a combination of ion-exchange chromatography, treatment with protease and chondroitin ABC lyase, and affinity fractionation with AT III. HSact and HSinact have molecular sizes of about 25-30 kDa with the same overall composition of monosaccharides except that HSact exhibits about nine glucuronsyl 3-O-sulfated glucosamines/chain whereas HSinact possesses about three glucuronsyl 3-O-sulfated glucosamines/chain. Direct isolation of the AT III-binding site of HSact by exposing carbohydrate chains to Flavobacterium heparitinase in the presence of protease inhibitor revealed only a single interaction site which contained two to three glucuronsyl 3-O-sulfated glucosamine residues. The core proteins of HSPGact and HSPGinact were isolated by treatment with Flavobacterium heparitinase and purification by ion-exchange chromatography. The molecular sizes of the core proteins were established by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and their primary structures were examined by cleavage with trypsin or endopeptidase Glu-C as well as separation of peptides by reverse-phase high performance liquid chromatography. The results showed that both sets of core proteins exhibited three major components with molecular sizes of 50, 30, and 25 kDa, respectively. The 25-kDa species appears to be a proteolytic degradation product of the 30-kDa species. The peptide mapping revealed that HSPGact and HSPGinact possess extremely similar core proteins.
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PMID:Isolation and characterization of heparan sulfate proteoglycans produced by cloned rat microvascular endothelial cells. 153 64

From rat brain, a membrane bound substance P-degrading endopeptidase (SPE) was purified 1580 fold to near homogeneity. After extraction with 10 mM CHAPS, the enzyme preparation was subjected to ion exchange chromatography on DEAE-cellulose, adsorption chromatography on hydroxyapatite, gelfiltration through Ultrogel AcA 44 and FPLC on Mono Q. This enzyme of 70,000 molecular weight is optimally active at pH 7.5. Metal chelators (EDTA and EGTA) and sulfhydryl modifying reagents (N-ethylmaleimide and p-chloromercuriphenylsulfonic acid) are strongly inhibitory while the serine-protease inhibitor diisopropyl-fluorophosphate does not effect the enzyme activity. The enzyme is strongly inhibited by bacitracin but not by phosphoramidon and captopril. Degradation of substance P is strongly inhibited by neurotensin, somatostatin, ACTH 1-39, and less effectively by LHRH but not by Leucine-enkephalin. Substance P is preferentially hydrolyzed at the Gln6-Phe7 peptide bond but fragmentation at the Pro4-Gln5, Gln5-Gln6,Phe7-Phe8 and Gly9-Leu10 bonds was also observed.
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PMID:A membrane bound substance P degrading endopeptidase from rat brain. 244 28

The primary structure of a 9-kDa basic protein from rice seeds was determined by gas-phase sequencing of the intact protein and peptides derived from it by digestion with trypsin, chymotrypsin, and endopeptidase Lys-K. The protein consists of a single polypeptide chain of 91 amino acid residues with a calculated molecular mass of 8909 Da. It is rich in alanine, serine, glycine, and cysteine. The eight cysteines form four disulfide bonds. There is no methionine, histidine, phenylalanine, or tryptophan. The sequence is highly homologous with an alpha-amylase inhibitor, I-2, from seeds of Indian finger millet [F. A. P. Campos and M. Richardson (1984) FEBS Lett. 167, 221-225] and a 10-kDa barley seed protein, also called a probable amylase/protease inhibitor [B. Svensson et al. (1986) Carlsberg Res. Commun. 51, 493-500; J. Mundy and J. C. Rogers (1986) Planta 169, 51-63]. In analogy with the barley protein, the purified protein is tentatively called a rice probable amylase/protease inhibitor (PAPI). The rice PAPI does not show inhibitory activities against proteases and amylases tested. The amino acid sequence is as follows: Ile-Thr-Cys-Gly-Gln-Val-Asn-Ser-Ala-Val(10)-Gly-Pro-Cys-Leu-Thr-Tyr- Ala-Arg-Gly-Gly(20)-Ala-Gly-Pro-Ser-Ala-Ala-Cys-Cys-Ser-Gly(30)-Val-Arg- Ser-Leu-Lys-Ala-Ala-Ala-Ser-Thr(40)-Thr-Ala-Asp-Arg-Arg-Thr-Ala-Cys- Asn-Cys(50)-Leu-Lys-Asn-Ala-Ala-Arg-Gly-Ile-Lys-Gly(60)-Leu-Asn-Ala-Gly- Asn-Ala-Ala-Ser-Ile-Pro(70)-Ser-Lys-Cys-Gly-Val-Ser-Val-Pro-Tyr-Thr(80)- Ile-Ser-Ala-Ser-Ile-Asp-Cys-Ser-Arg-Val-Ser(91).
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PMID:Amino acid sequence of a probable amylase/protease inhibitor from rice seeds. 245 99

The generation of angiotensin I from the artificial renin substrate tetradecapeptide by proteolytic enzymes in rat brain tissue was studied. The involvement of endopeptidase activity in the enzymatical cleavage of the renin substrate was inferred from the simultaneous accumulation of both angiotensin I and the complementary tetrapeptide Leu-Val-Tyr-Ser on incubation of tetradecapeptide with rat brain tissue. This endopeptidase activity was active over a pH range of 3.5--7.5. In contrast, cathepsin D released angiotensin I from tetradecapeptide only at acidic pH. The angiotensin I accumulation on incubation of tetradecapeptide with brain endopeptidase activity was only partly inhibited in the presence of an excess of the carboxyl protease inhibitor N-acetyl pepstatin. Further, the brain endopeptidase activity displayed a subcellular localization different from that of acid protease activity. It is concluded that angiotensin I can be generated in the brain by soluble endopeptidases, which are distinct from cathepsin D.
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PMID:Subcellular localization in rat brain of angiotensin I-generating endopeptidase activity distinct from cathepsin D. 703 49

1. We have previously shown that atrial natriuretic peptide causes bronchodilatation and reduces bronchial reactivity when administered intravenously or by inhalation to asthmatic patients. We wished to determine the direct effect of exogenously applied atrial natriuretic peptide on isolated airway and the role of proteases important in atrial natriuretic peptide degradation in other organ systems. 2. The ability of atrial natriuretic peptide (alpha-human atrial natriuretic peptide 28-amino acid) to relax precontracted tissues and to protect against methacholine-induced contraction was studied in human and bovine tissue. The role of neutral endopeptidase-24.11 and other proteases in regulating the effect of atrial natriuretic peptide on bronchial smooth muscle was also examined by studying the influence of phosphoramidon, a protease inhibitor, whose actions include the inhibition of neutral endopeptidase-24.11, and the protease inhibitors leupeptin, aprotinin and soybean trypsin inhibitor on the airway response to atrial natriuretic peptide. 3. In human and bovine tissue atrial natriuretic peptide (10(-6) mol/l) caused a slight relaxation of methacholine-contracted tissue [mean (SEM) percentage inhibition of contraction of 13.2 (3.02)% and 9.41 (2.63)% respectively] and evoked a significant rightward shift of the cumulative concentration-response curve to methacholine [pD2 5.15 (0.23) and 4.85 (0.1) compared with control values of 6.14 (0.1) and 5.85 (0.16), respectively]. 4. Phosphoramidon potentiated atrial natriuretic peptide-induced relaxation of methacholine-induced tone and the ability of atrial natriuretic peptide to protect against methacholine-induced contraction. The combination of leupeptine, aprotinin and soybean trypsin inhibitor did not significantly alter the bronchial response to atrial natriuretic peptide in either human or bovine tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of the effect of atrial natriuretic peptide in human and bovine bronchi by phosphoramidon. 751 55

The beta-amyloid precursor protein (beta-APP) is a membrane spanning glycoprotein. The small beta-protein domain within the precursor is presumed to be the source of amyloid found in plaques characteristic of Alzheimer's disease. The amino terminus of beta-APP is released from cells by cleavages that produce both potentially amyloidogenic and nonamyloidogenic fragments of the carboxyl terminus. We developed a cell free system that imposes specificity and co-localization to characterize the proteolytic activity that cleaves the precursor within the beta-protein domain. A reporter protein containing the carboxyl-terminal 105 amino acids of beta-APP provided a specific substrate for cleavage at Lys16 of the beta-protein. The protease inhibitor profile and solubility characteristics of the activity demonstrate the cleavage is produced by an integral membrane metalloendopeptidase.
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PMID:Non-amyloidogenic cleavage of the beta-amyloid precursor protein by an integral membrane metalloendopeptidase. 830 Jun 47

The released neutrophil chemotactic activity (NCA) from bronchial epithelial cells (BECs) in response to smoke extract was evaluated by reverse-phase, high-performance liquid chromatography (RP-HPLC) and the involvement of proteolytic activity was assessed for the release of NCA from BECs. Smoke extract stimulated the release of NCA (55.3 +/- 5.2 vs. 17.3 +/- 4.1 cells per high-power field [HPF], p < .001). The released activity determined by RP-HPLC analysis was 15-hydroxyeicosatetraenoic acid and leukotriene B4. Several structurally and functionally different serine protease inhibitors, including alpha-1-protease inhibitor (alpha-1-PI), chloromethyl ketone (CK) derivatives, N-tosyl-L-lysine CK (TLCK), methoxysuccinyl-Ala-Ala-Pro-Val CK (SPCK), N-alpha-tosyl-L-phenylalanine CK (TPCK), and N-alpha-p-tosyl-L-arginine methyl ester hydrochloride (TAME), attenuated the release of NCA (P < .01) in a dose-dependent fashion. Leupeptin, a cysteine protease inhibitor, has only a small effect on the release of NCA (p < .05), and phosphoramidon, a neutral endopeptidase inhibitor, had no effect. The measurement of proteolytic enzyme activity using synthetic substrate S-2288 revealed that smoke extract significantly (p < .05) augmented the serine protease activity in BEC layers. Culture supernatant fluids and cell lysates of BECs in response to smoke extract solubilized 14C-labeled casein. These results suggest that BECs may release lipoxygenase-derived NCA in response to smoke extract and that the release of NCA may involve the activation of proteolytic activity of BECs which was inhibited by serine protease inhibitors.
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PMID:Antiproteases attenuate the release of neutrophil chemotactic activity from bronchial epithelial cells induced by smoke. 883 32

The new chromatographic system Akta-Purifier 10 (Amersham-Pharmacia Biotech), scaled for preparative HPLC, was used for the purification of Substance P (SP) endopeptidase activity in the ventral tegemental area (VTA) of the rat brain. SP endopeptidase previously identified and purified from human cerebrospinal fluid has been found to degrade the neuroactive peptide SP in a specific pattern. In this study we have recovered SP endopeptidase from the rat VTA following a purification scheme involving homogenization (ultrasonication) and extraction of the excised tissue, size-exclusion chromatography (Superdex 75 HR), and ion-exchange chromatography (Resource Q). In this way we were able to achieve a purification factor of almost 7,500, based on specific activity. The obtained SP endopeptidase activity, was then subjected to characterization with regard to inhibition profile. The enzyme activity was monitored by following the conversion of SP to its N-terminal fragment SP(1-7) using a radioimmunoassay, specific for the heptapeptide product. On basis of inhibition profile it was possible to discern two different SP endopeptidase-like activities, one sensitive toward the protease inhibitor phosphoramidon (preparation A), and another non-sensitive to phosphoramidon or captopril (preparation B). The molecular masses of preparations A and B, as derived from sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were found to be 90,000 and 76,000, respectively. Our data suggest that the purified phosphoramidon sensitive endopeptidase activity may be an enzyme that plays a major role in the conversion of SP to its bioactive fragment SP(1-7) in the rat VTA. This is likely to be identical to the previously known neutral endopeptidase (EC 3.4.24.11). However, this study also demonstrates the existence of a distinct endopeptidase activity with properties in agreement with rat spinal cord SP endopeptidase. In the context of previously shown altered levels of SP(1-7) in the VTA during morphine withdrawal both purified enzyme activities may turn out to be responsible.
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PMID:Purification of substance P endopeptidase activity in the rat ventral tegemental area with the Akta-Purifier chromatographic system. 1104 91

Dipeptidyl peptidase I (DPPI) or cathepsin C is the physiological activator of groups of serine proteases from immune and inflammatory cells vital for defense of an organism. The structure presented shows how an additional domain transforms the framework of a papain-like endopeptidase into a robust oligomeric protease-processing enzyme. The tetrahedral arrangement of the active sites exposed to solvent allows approach of proteins in their native state; the massive body of the exclusion domain fastened within the tetrahedral framework excludes approach of a polypeptide chain apart from its termini; and the carboxylic group of Asp1 positions the N-terminal amino group of the substrate. Based on a structural comparison and interactions within the active site cleft, it is suggested that the exclusion domain originates from a metallo-protease inhibitor. The location of missense mutations, characterized in people suffering from Haim-Munk and Papillon-Lefevre syndromes, suggests how they disrupt the fold and function of the enzyme.
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PMID:Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases. 1172 93


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