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)

Some properties (molecular weight, pI, temperature stability, action of selected inhibitors, substrate specificity and pH-activity dependence) of two not yet known cathepsins from rat liver lysosomes are compared with the properties of the known cathepsin B1. Cathepsin L is a thiolproteinase, has a molecular weight of 23--24000 and a pI of 5,8--6,1. By disc electrophoresis and isoelectric focusing there appear several protein bands which all have enzymatic activity. Leupeptin behaves as a strong inhibitor. The pH-optimum for digestion of proteins is close to 5,0. Cathepsin L does not hydrolyse esters and splits synthetic low molecular substrates only to a low degree. Cathepsin L stored in presence of glutathion and EDTA in liquid nitrogen kept its activity for some months. Cathepsin H is an aminopeptidase as well as an endopeptidase. An enzyme with these bifunctional properties was detected up to now only in E. coli but not in animal cells. Cathepsin H is a thiol-enzyme with a molecular weight of 28000 and a pI of 7,1. Strong inhibitors are leucyl-chlormethan and SH-blocking substances. Leupeptin shows only a weak inhibitory effect to this enzyme compared to its action on cathepsins L and B1. The pH-optimum for hydrolysis of all substrates is 6.0. Cathepsin H splits proteins, amino acid derivatives and selected N-protected amino acid derivatives. Cathepsin H compared to cathepsin L and B1 is quite temperature stable.
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PMID:[Intracellular protein breakdown. VII. Cathepsin L and H; two new proteinases from rat liver lysosomes]. 0 66

Our previous studies indicated that Arginine (Arg) plays a key nutritional role in Streptococcus sanguis P4A7 and that this organism can grow on whole casein as the sole nitrogen source. Its protease activities were therefore studied after glucose-limited continuous culture in a chemically-defined medium with either free amino acids or casein as the nitrogen source. Both culture supernatant and cell-associated endopeptidase (EP) and exopeptidase (amino-AP and carboxy-CP) activities were determined. Growth rate (mu) had little effect on EP, 75% of which was consistently in culture supernatants; AP and CP both decreased as mu was increased and both were predominantly cell-associated. At high growth pH, EP was substantially increased while AP and CP activities were optimal at pH 7. The most striking nutritional effect occurred under nitrogen limitation (glucose excess) when EP and AP were greatly increased and CP greatly decreased. It was concluded that S. sanguis is well equipped to scavenge its environment for Arg under a wide range of growth conditions.
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PMID:Some aspects of protease production by a strain of Streptococcus sanguis. 208 51

Human cultured T lymphocytes of the Jurkat line and myeloma cells of the U266 line cleaved the 28 amino acid vasoactive intestinal peptide (VIP1-28) preferentially at three sites with time- and temperature-dependence. The fragments VIP4-28 and VIP23-28) from an endopeptidase activity, and VIP15-28 from a trypsin-like peptidase, together represented a range of 26-65% of the VIP1-28 recovered after 2 hr at 37 degrees C or 4 hr at 22 degrees C, based on the absorbance of purified peptides and the radioactivity of [125I]Tyr10 VIP1-28. The endopeptidase activity was associated with membranes recovered after disruption of U266 cells by nitrogen cavitation. Pretreatment of intact U266 and Jurkat cells with diisopropylfluorophosphate (DFP) and the subsequently isolated subcellular particles with phenylmethylsulphonylfluoride (PMSF) and leupeptin inhibited the trypsin-like enzyme by a mean of 80%, without suppressing endopeptidase activity. In contrast, 0.1 mM DL-thiorphan and phosphoramidon blocked selectively a range of 35-70% of the endopeptidase activity in membrane preparations and intact cells. The capacity of lymphocytes to degrade VIP1-28 may substantially alter the effects of this neuromediator on functions of some subsets of T and B cells.
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PMID:Unique pattern of cleavage of vasoactive intestinal peptide by human lymphocytes. 265 11

Mutants deficient in the vacuolar (lysosomal) endopeptidases proteinase yscA and proteinase yscB of the yeast Saccharomyces cerevisiae exhibit a drastically reduced protein degradation rate under nutritional stress conditions. The differentiation process of sporulation is considerably disturbed by the absence of the two endopeptidases. Also under vegetative growth conditions and under conditions of false protein synthesis, the two vacuolar endopeptidases exhibit some effect on protein degradation, which is, however, much less pronounced as found under starvation conditions. Proteinase yscA deficiency leads to rapid cell death when glucose-grown cells starve for nitrogen or other nutrients. Whereas overall protein degradation is affected in the endopeptidase mutants, degradation of two distinct false proteins analyzed is not altered in the absence of proteinase yscA and proteinase yscB. Also catabolite inactivation and degradation of fructose-1,6-bisphosphatase is not affected to a greater extent in the endopeptidase-deficient strains.
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PMID:Lysosomal (vacuolar) proteinases of yeast are essential catalysts for protein degradation, differentiation, and cell survival. 267 23

The three-dimensional structures of (S)-thiorphan and (R)-retro-thiorphan bound to thermolysin have been determined crystallographically and refined to residuals of 0.183 and 0.187 at 1.7-A resolution. Thiorphan [N-[(S)-2-(mercaptomethyl)-1-oxo-3-phenylpropyl]glycine] [HSCH2CH(CH2C6H5)CONHC-H2COOH] and retro-thiorphan [[[(R)-1-(mercaptomethyl)-2-phenylethyl] amino]-3-oxopropanoic acid] [HSCH2CH(CH2C6H5)NHCOCH2COOH] are isomeric thiol-containing inhibitors of endopeptidase EC 24-11 (also called "enkephalinase"). The mode of binding of thiorphan to thermolysin is similar to that of (2-benzyl-3-mercaptopropanoyl)-L-alanylglycinamide [Monzingo, A.F., & Matthews, B.W. (1982) Biochemistry 21, 3390-3394] with the inhibitor sulfur atom coordinated to the active site zinc and the peptide portion forming substrate-like interactions with the enzyme. The isomeric inhibitor retro-thiorphan, which differs from thiorphan by the inversion of an amide bond, utilizes very similar interactions with enzyme. Despite the inversion of the -CO-NH- linkage the carbonyl oxygen and amide nitrogen display very similar hydrogen bonding, as anticipated by B.P. Roques et al. [(1983) Proc. Natl. Acad. Sci. U.S.A. 80, 3178-3182]. These results explain why thermolysin and possibly other zinc endopeptidases such as endopeptidase EC 24-11 fail to discriminate between these retro-inverso inhibitors.
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PMID:Thiorphan and retro-thiorphan display equivalent interactions when bound to crystalline thermolysin. 271 12

Ten peptides were tested as substrates for cathepsin I. The enzyme exerted both endopeptidase and aminopeptidase activities on 5 substrates, only aminopeptidase activity on 3 others, and only endopeptidase cleavage on one compound. One peptide was not significantly hydrolyzed. Aminopeptidase activity stopped one residue before a proline residue and endopeptidase cleavage took place one residue after a proline residue. With these substrates, this enzyme appears to have a broad specificity in its aminopeptidase action. However, cathepsin I appears to have a much narrower and more specific endopeptidase activity, hydrolyzing peptide bonds involving the nitrogen of branched chain or bulky or hydrophobic amino acids. Finally, some differences in the physical, chemical and biological properties of cathepsins H and I were discussed.
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PMID:The specificity of rabbit lung cathepsin I on biopeptides. 357 72

1. Peptidase extracted with buffer at pH5.2 from small samples of tobacco-leaf tissue was assayed by measuring the alpha-amino nitrogen liberated from gelatin at 40 degrees in 1hr. The rate of hydrolysis was constant during the digestion. 2. The inclusion of sodium thioglycollate (60mm) in the extracting medium increased the activity of the peptidase. 3. As the major products of hydrolysis were peptides, the enzyme is an endopeptidase. 4. The decrease in protein observed in leaves with increasing physiological age and with time after harvest is correlated with increase in specific activity of peptidase in extracts from the leaves.
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PMID:Activity of peptidase in tobacco-leaf tissue in relation to senescence. 588 63

Proline-containing polypeptides are shown to be sequentially degraded by two aminopeptidases. Clostridial aminopeptidase (EC 3.4.11-) cleaves off any N-terminal amino acid residue including proline from polypeptide chains, but does not cleave the N-terminal secondary peptide bonds involving a prolyl nitrogen. Aminopeptidase P (EC 3.4.11.9) cleaves exclusively such secondary bonds. The two enzymes were immobilized by coupling them covalently to porous amino glass beads. Highly stable preparations were obtained with unchanged pH optimum and thermal stability. The applicability of clostridial aminopeptidase to sequence determination was demonstrated by the time-dependent hydrolysis of enkephalin and Substance P octapeptide. Sequential hydrolysis with the two immobilized enzymes was demonstrated with the proline-containing (Pro-Gly-Pro)10, [Asn1, Val5]angiotensin II, bradykinin, Substance P and tuftsin. Absence of endopeptidase activities was demonstrated by resistance of cytochrome c to hydrolysis and by the ordered release of amino acids during the sequential degradation by immobilized clostridial aminopeptidase and aminopeptidase P.
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PMID:Sequential hydrolysis of proline-containing peptides with immobilized aminopeptidases. 683 Aug 20

1. In this study, we sought to determine the effect of endopeptidase 24.11 inhibition on the rate of metabolism of vasoactive intestinal peptide. The effect of such inhibition on the concentration of vasoactive intestinal peptide in two tissues was also investigated. 2. Male Sprague-Dawley rats were given the endopeptidase 24.11 blocker UK77,568 (10 mg/kg) or vehicle as a single intravenous injection or as a daily injection for 4 days. Two hours after the final or single injection, the rats were anaesthetized and blood was sampled to determine plasma concentrations of vasoactive intestinal peptide and angiotensin II. The hearts and kidneys were harvested and snap-frozen in liquid nitrogen. The plasma and tissue concentrations of vasoactive intestinal peptide and the plasma concentration of angiotensin II were determined by radioimmunoassay. In a separate group of experiments, male Sprague-Dawley rats were anaesthetized and carotid and jugular catheters were inserted. One hour after intravenous administration of UK77,568 or vehicle, an infusion of vasoactive intestinal peptide (10 pmol min-1 kg-1) was commenced via the jugular catheter. Blood was sampled to determine the vasoactive intestinal peptide concentration 1 h after commencing the vasoactive intestinal peptide infusion to calculate the metabolic clearance rate. 3. Plasma vasoactive intestinal peptide increased after acute (P < 0.05) but not chronic administration of UK77,568, while the concentration of vasoactive intestinal peptide in the heart increased after chronic administration (P < 0.0005). The concentration of vasoactive intestinal peptide in the kidney was unchanged after both acute and chronic endopeptidase 24.11 blockade. Plasma angiotensin II decreased significantly in the chronic group (P<0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of endopeptidase 24.11 inhibition on plasma and tissue concentrations of vasoactive intestinal peptide. 749 22

Adamalysin II, alias proteinase II, a 24 kDa zinc-endopeptidase isolated from the snake venom of the Eastern diamondback rattlesnake Crotalus adamanteus, is a prototype of the proteolytic domain of snake venom metalloproteinases and of domains found in mammalian reproductive tract proteins. Its 2.0 A crystal and molecular structure was solved by multiple isomorphous replacement using six heavy-atom derivatives, and was refined to a crystallographic R-value of 0.172. 201 of the 203 amino acid residues of adamalysin II are defined by electron density; only the first two residues are disordered and crystallographically undefined in the crystal structure. Three-quarters of these crystallographic amino acid residue assignments were confirmed by chemical sequencing. In addition, the active-site zinc-ion, a hepta-coordinated calcium ion, a fixed sulphate anion and 173 solvent molecules were localized in the structure. Adamalysin II is an ellipsoidal molecule with a relatively flat active-site cleft separating the "upper" main body from a small "lower" subdomain. The regularly folded N-terminal upper domain consists essentially of a central, highly twisted five-stranded beta-pleated sheet flanked by a long and a short surface located helix on its convex side, and by two long helices, one of which represents the central "active site helix", on its concave side. The lower subdomain, comprising the last 50 residues, is organized in multiple turns, with the chain ending in a long C-terminal helix and an extended segment clamped to the upper domain via a disulphide bridge. The catalytic zinc-ion, located at the bottom of the active-site cleft, is almost tetrahedrally co-ordinated by His142, His146 and His152, and a water molecule anchored to an intermediate glutamic acid residue (Glu143), with the three imidazole N epsilon 2 nitrogen atoms 2.1 A and the solvent oxygen atom 2.4 A away from the zinc ion. His142, Glu143 and His146 are part of the long active-site helix, which extends up to Gly149, where it turns sharply away towards His152. The importance of these residues for structure and activity of adamalysin II explains their occurrence in the HEXXHXXGXXH consensus sequence. Asp153, which is strictly conserved in these snake venom and reproductive tract metalloproteinases, is buried in the subdomain and seems to stabilize the hydrophobic active-site basement. Some residues behind, the adamalysin peptide chain folds into a characteristic 1,4-turn (the "Met-turn") containing the conserved Met166, which forms a hydrophobic basement for the three zinc-binding imidazoles.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Refined 2.0 A X-ray crystal structure of the snake venom zinc-endopeptidase adamalysin II. Primary and tertiary structure determination, refinement, molecular structure and comparison with astacin, collagenase and thermolysin. 800 65


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