Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is known that the negatively stained preparations of inner mitochondrial membrane display characteristic approximately 9 nm F1 (ATPase) knobs projecting from the matrix surface. Freeze-etch studies have reported the absence of such knobs from the "etched" surface of the inner mitochondrial membranes. We have demonstrated their presence on the surface of SMP (submitochondrial particles) prepared by freeze-drying for transmission electron microscopy. This identification has been substantiated by comparison with freeze-dried TU particles (trypsin-urea treated SMP) that are devoid of F1 (ATPase). It has been suggested that a layer of water molecules is strongly adsorbed to the surface of SMP and does not sublime during normal freeze-"etching."
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PMID:Visualization of mitochondrial coupling factor F1(ATPase) by freeze-drying. 9 68

The papain inhibitor isolated from chicken egg white inhibits the enzymatic activity of cathepsin B1 and cathepsin C. The inhibitor bears two nonoverlapping reactive sites: one binds cathepsin B1, papain, ficin, and bromelain, the other one cathepsin C. The inhibitor decreases the degree of an immunologic hypersensitive reaction, the so-called Arthus reaction. A statistically significant inhibition of this immunologically developed inflammation occurs only if the inhibitor is applied intradermally and simultaneously with the provoking dose of the antigen to rabbits sensitized to the same antigen. The pepsin inhibitor from the body walls of the roundworm Ascaris lumbricoides inhibits the proteolytic activity of cathepsin E. This inhibitor covalently bound to Sepharose 4B was used for affinity chromatography of cathepsin E. A cathepsin D inhibitor was isolated from potato tubers and its inhibitory and chemical characteristics were studied. The inhibitor does not inhibit either cathepsin E or pepsin yet inhibits trypsin in the alkaline pH-range. The molecular weight of the inhibitor is 21 790 and its molecule consists of 199 amino acid residues. The sequence of 17 amino acid residues was determined by Edman degradation of the inhibitor molecule.
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PMID:Naturally occurring inhibitors of intracellular proteinases. 61 34

Located close to the crown of the V3 type-specific neutralization loop of the human immunodeficiency virus type 1 (HIV-1) (IIIB) SU glycoprotein gp120, are several potential sites that should be susceptible to proteolytic cleavage by enzymes of trypsinlike or chymotrypsinlike specificity, or by aspartic proteinases. The linkages potentially sensitive to chymotryptic/aspartic proteinase cleavage are retained also within the equivalent domain of HIV-2 (ROD) gp105. We show that thrombin and tryptase cleave HIV-1 gp120 specifically at the tryptic site (GPGR decreases AFVT), and that cathepsin E, an endosomal aspartic proteinase, cleaves at the chymotrypsinlike site (GPGRAF decreases VT). HIV-2 gp105 is also cut by cathepsin E at a site (QIML decreases MSGH) in its V3 loop. Cleavage of HIV-1 gp120 by thrombin is enhanced by sCD4 binding, but is prevented by transient exposure of gp120 to nonionic detergent. Thrombin treatment of HIV-1 gp120 destroys the binding sites for some neutralizing monoclonal antibodies (MAbs) on the V3 loop, but does not affect the affinity of gp120 for sCD4. Conversely, binding of neutralizing MAbs to the HIV-1 V3 loop prior to addition of thrombin or cathepsin E blocks the cleavage reactions, and the binding of some HIV-positive sera to gp120 blocks thrombin cleavage. Analysis of published sequences suggests that all HIV-1, HIV-2, and simian immunovirus (SIV) isolates contain potential proteolytic cleavage sites at similar positions in their V3 loops or equivalent domains. We suggest that cleavage of the V3 loop by a cell surface or endosomal proteinase occurs during the HIV-cell fusion reaction, and that neutralizing antibodies directed against the V3 loop might act by inhibition of this reaction.
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PMID:The V3 loops of the HIV-1 and HIV-2 surface glycoproteins contain proteolytic cleavage sites: a possible function in viral fusion? 201 14

Smooth muscle phosphatase-I (SMP-I), a protein phosphatase purified from turkey gizzard smooth muscle, is composed of 2 regulatory subunits (Mr = 60,000 and 55,000) and a catalytic subunit (Mr = 38,000). Two other forms of this enzyme have been prepared and characterized. The free catalytic subunit, termed SMP-Ic, was prepared by ethanol treatment of SMP-I, and a form devoid of the 55,000-Da subunit, termed SMP-I2, was prepared by limited tryptic digestion. Exposure of SMP-I to proteases like trypsin and chymotrypsin results in a rapid degradation of the 55,000-Da polypeptide. Degradation of the catalytic subunit is observed only upon prolonged digestion. The 60,000-Da polypeptide appears to be resistant to the action of trypsin and chymotrypsin. SMP-I dephosphorylates myosin light chains but is not active toward intact myosin or heavy meromyosin. However, when the catalytic subunit is dissociated from both regulatory subunits or from the 55,000-Da polypeptide, the enzyme becomes active toward myosin suggesting that the 55,000-Da polypeptide inhibits the activity of the catalytic subunit toward myosin. In addition to alteration of the substrate specificity, the regulatory subunits also modulate the effect of divalent cations, like Mn2+, on the activity of the enzyme.
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PMID:Limited proteolytic digestion and dissociation of smooth muscle phosphatase-I modifies its substrate specificity. Preparation and properties of different forms of smooth muscle phosphatase-I. 300 99

The complement fixing antigen of the inner mitochondrial membrane previously shown to be associated with the mitochondrial ATPase could be further purified by subjecting the ATPase extracted from beef heart and brown fat mitochondria to ion exchange and gel filtration chromatography. Although the ATPase activity could be clearly dissociated from the complement fixing activity, subunits of the F1-ATPase complex were always found in the purified fractions. The alpha, gamma, delta and epsilon subunits of the complex could be excluded with high probability as target antigens in contrast to the beta band which was always found in association with the antigen activity. These findings imply that the active centre of the ATPase enzyme is not involved in the antibody reaction but molecules of the ATPase complex may have antigen binding capacity. Treatment of ATPase associated antigen with trypsin did not markedly affect the complement binding, while SMP's treated in the same way lost their antigen activity indicating that sera from patients with primary biliary cirrhosis (PBC) may have mitochondrial antibodies of different specificities reacting with trypsin sensitive as well as trypsin insensitive components of the inner membrane. The purified antigen reacted exclusively with sera from patients with PBC and may be therefore used as a marker antigen.
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PMID:Mitochondrial antibodies in primary biliary cirrhosis. VI. Association of the complement fixing antigen with a component of the mitochondrial F1-ATPase complex. 618 57

Cathepsin E (CE) is an endosomal aspartic proteinase of the A1 family that is highly homologous to the lysosomal aspartic proteinase cathepsin D (CD). Newly synthesized CE undergoes several proteolytic processing events to yield mature CE, from which the N-terminal propeptide usually comprising 39 amino acids is removed. To define the role of the propeptide of CE in its biosynthesis and processing, we constructed two fusion proteins using chimeric DNAs encoding the CE propeptide fused to the mature CD tagged with HA at the COOH terminus (termed ED-HA) and encoding the CD propeptide fused to the mature CE (termed DE). Pulse-chase analysis revealed that wild-type CE expressed in human embryonic kidney cells is autoproteolytically processed into mature CE within a 12-h chase, whereas the chimeric DE failed to be converted into mature CE even after a 24-h chase. The DE chimera was nevertheless capable of acid-dependent autoactivation in vitro to yield a catalytically active form, although its specificity constants (kcat/Km) were considerably high but less (35%) than those of the wild-type CE. By contrast, the chimeric ED-HA expressed in HeLa cells underwent neither processing into a catalytically active enzyme nor acid-dependent autoactivation in vitro. The ED-HA protein was less stable than wt-CD-HA, as determined on pulse-chase analysis and on trypsin digestion. These data indicate that the propeptide of CE is essential for the correct folding, maturation, and targeting of this protein to its final destination.
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PMID:The role of the cathepsin E propeptide in correct folding, maturation and sorting to the endosome. 1627 74

This study investigated the pruritogenic potency of cathepsin E, an aspartic protease, and its mechanisms in mice. An intradermal injection of cathepsin E to the rostral back elicited scratching, an itch-associated response, of the injection site. This action was inhibited by the aspartic protease inhibitor pepstatin A, the endothelin ET(A) receptor antagonist BQ-123, and the opioid receptor antagonists naltrexone and naloxone, but not by the H(1) histamine receptor antagonist terfenadine, the proteinase-activated receptor-2 antagonist FSLLRY-NH(2), or mast cell deficiency. Pepstatin A inhibited scratching induced by intradermal injection of the mast-cell degranulator compound 48/80, but not by tryptase, a mast-cell mediator. An intradermal injection of cathepsin E increased endothelin-1 levels in the skin at the injection site. Preproendothelin-1 mRNA was present in primary cultures of keratinocytes, and immunohistochemistry using an antibody recognizing endothelin-1 and big-endothelin-1 revealed immunoreactivity in the epidermis, especially in the prickle and granular cell layers, but not in the basal cell layer. These results suggest that cathepsin E is an endogenous itch inducer, and that its action is mediated at least in part by the production of endothelin-1 in the epidermis.
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PMID:Cathepsin E induces itch-related response through the production of endothelin-1 in mice. 2254 26