Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By isoelectric focusing, we separated trypsin-like proteinases of the mouse submandibular gland (ICR strain) into isozymes with pI values of 4.6 (proteinase F), 5.6 (protease D), 5.8 (protease A), 7.1 and 9.9 (P-esterase). During postnatal development, proteinase F appeared earliest (on the 15th day after birth) and increased in both sexes; however, its percentage ratio to total activity decreased markedly with time because of the rapid increase of other proteinases. On the 22nd day of life, proteinases A and D appeared, and the increase of a proteinase with pI-7.1 followed thereafter. P-esterase was the last isozyme to appear, becoming detectable around 29-45 days. After maturation, the activities of protease A plus D, P-esterase, and the isozyme with a pI value of 7.1 were higher in males than in females, whereas the relative level of proteinase F was reversed. We conclude that proteinase F is appreciably different from the other four proteinases in its development pattern as well as in its responsiveness to sexual hormones.
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PMID:Reversal of relative proteinase F activity and onset of androgen-dependent proteinases in the submandibular gland of postnatal mice. 228 78

Lectin binding to formalin-fixed, paraffin-embedded tissue can often be enhanced by pre-treatment of the sections with proteolytic enzymes. However, the pattern of staining may be profoundly influenced by the type of enzyme preparation which is used. Sites of binding of thirteen different lectins to murine ovary and thyroid gland were studied after exposure of tissue sections to crude trypsin, purified trypsin, purified alpha-chymotrypsin, pepsin, protease VII, papain, bromelain, thermolysin or elastase. With most lectins, the results obtained were similar regardless of which enzyme was used for proteolytic digestion. However, the pattern of binding of soy bean lectin to the ovary and of concanavalin A and common pea lectin to the thyroid gland was highly dependent upon the enzyme used to pre-treat the sections. In both tissues, the staining pattern seen in untreated frozen sections was similar to that found in formalin-fixed, paraffin-embedded material digested with purified trypsin, but was different from that observed after exposure of processed sections to crude trypsin. The location of binding sites after treatment of paraffin sections with chymotrypsin was the same as that after digestion with crude trypsin. Results obtained after the use of other proteolytic enzymes varied according to the tissue being studied. These findings imply that the effect of treatment with crude trypsin is due to contaminating chymotrypsin, and demonstrate that the use of purified trypsin may have advantages over other proteolytic enzymes in lectin histochemistry. The observations may also apply to other related cytochemical techniques such as immunocytochemistry.
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PMID:Proteolysis and lectin histochemistry. 244 Aug 34

In this paper, I attempt to summarize the main qualitative features of electrostatic complementarity and similarity, important determinants of molecular recognition. The two aspects, Coulombic and hydrophobic matching, can be formulated in terms of molecular electrostatic potentials and fields. The Coulombic aspect is equivalent to the requirement to produce a potential pattern in the host cavity that is opposite in sign to that emerging from a guest. Hydrophobic complementarity is best described by the similis simili gaudet principle. This means that field patterns near the interacting molecular surfaces must be of similar magnitude. The above rules, which may find useful application in molecular graphics, were studied for different cases of enzyme-ligand interactions in trypsin. A further example, a noncovalent structural model of the catalytic diad in Streptomyces Griseus protease A, supports the observation that the same molecular entities form similar associations even in different environments, as is the case in the complex of small species in a crystal and amino acid residues with structural water molecules in a protein.
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PMID:Electrostatic complementarity in molecular associations. 248 67

1. Four cyclic AMP phosphodiesterase-activating activities, designated as A, B, C and D, were isolated from lugworm, Arenicola cristata, by preparative flat-bed isoelectric focusing. Activators C and D were further purified by TSK 3000SW HPLC to homogeneity. 2. Activators A, B, C, and D corresponded to pIs of 4.4, 5.0, 5.2 and 5.4; their mol wts were estimated to be 36,200, 30,500, 30,200 and 28,300 respectively. 3. The protease nature of these activities were confirmed by the inhibition by several trypsin inhibitors of their activation of phosphodiesterase and by their hydrolysis of TAME, a synthetic trypsin substrate. Only protease A also hydrolyzed BTEE, a chymotrypsin substrate.
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PMID:Isolation from lugworm (Arenicola cristata) of four proteases that activate cyclic AMP phosphodiesterase. 282 20

Three major esteroproteases, proteases A and D and P-esterase, obtained from the glands were studied kinetically and chemically; two (proteases A and D) were identified. Protease A is composed of a single subunit, molecular weight (27,600) similar to the native molecule (27,000); protease D consists of three subunits, approximate molecular weights of 9200, 7600 and 4600. P-esterase contains two subunits, approximate molecular weights of 7100 and 14,000. Protease A exhibits a strong kinin-releasing activity; the other two enzymes have low activity. Protease D binds to low molecular weight-epidermal growth factor, forming a complex which has an electrophoretic mobility similar to that of high molecular weight-epidermal growth factors. When beta-nerve growth factor was incubated with protease A, the amino-terminal amino acid, serine, was lost from the growth factor and a new amino-terminal amino acid, methionine, appeared. These data indicate that proteases D and A are the same proteins as epidermal growth factor-binding protein and beta-nerve growth factor endopeptidase, respectively. From a comparison of the peptide maps of trypsin-digests of the enzymes, the proteases A and D were inferred to have a similar primary structure.
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PMID:Characterization of two esteroproteases from the male mouse submandibular gland. 630 36

A technique is described to detect the activity of protease inhibitors present in sodium dodecyl sulfate (SDS)-polyacrylamide gels (PAG) containing a copolymerized enzyme substrate. The method involved (1) incorporation of substrate (gelatin or casein) into the SDS-PAG at the time of casting; (2) electrophoresis of the protease inhibitors in the presence of SDS; (3) removal of SDS by washing the gel in 2.5% (w/v) Triton X-100; (4) incubation of the gels in a solution containing the proteolytic enzyme at 37 degrees C for 16 h; and (5) staining undigested substrate with amido black. Standard inhibitors such as bovine pancreatic trypsin inhibitor (BPTI), soybean trypsin inhibitor (SBTI), alpha 1-antitrypsin inhibitor, and a protease inhibitor derived from human articular cartilage have been examined by this method and displayed sharp inhibition bands when the gels were treated with bovine trypsin, chymotrypsin, or other enzymes. The technique cannot be used for precise quantification of protease inhibitors. However, there is a relationship between the concentration of inhibitor used and the intensity of staining. By this means, it was possible to estimate the smallest amount of inhibitor that could be detected (against a particular enzyme) under a given set of conditions. Inhibition was detected when 10 ng of SBTI or 20 ng of BPTI were applied to the gels; human alpha 1-protease inhibitor could be detected at a level of 2-3 micrograms. The technique was used to investigate the effectiveness of the human cartilage inhibitor against a variety of proteolytic enzymes, including thermolysin, Pronase, neutral protease, elastase, protease VII, pepsin, bacterial collagenase, protease IV, and papain.
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PMID:Detection of protease inhibitors using substrate-containing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 635 99

The split-off 1-2 short peptides is the first stop in the endogenous protease A effect on the vetch legumin, which results in a step-wise rise of its hydrolyzability by two other endogenous proteases (B and C). Short neutral and basic peptides are consecutively split off from the acid subunits in the course of subsequent hydrolysis by protease A, while the breakdown of these subunits into larger fragments, which are retained in the legumin molecule by non-covalent bonds, occurs later. Similar results were obtained in experiments on trypsin action of legumin. Thus the initial course of legumin hydrolysis is largely determined by its structure. The changes of legumin during germination are similar to those occurring upon limited proteolysis by protease A. However, some differences are indicative of the existence of other factors responsible for the modification of this protein during germination. The modification of vicilin during germination and limited proteolysis occurs apparently in a similar way.
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PMID:[Modification of vetch seed reserve proteins during germination and limited proteolysis]. 702 39

Apoptosis was induced in THP.1 cells, a human monocytic tumour cell line, by diverse stimuli including cycloheximide, thapsigargin, etoposide and staurosporine. Induction of apoptosis by all these stimuli, except etoposide, was enhanced in the presence of the trypsin-like protease inhibitor, N alpha-tosyl-L-lysinyl chloromethyl ketone (TLCK). Induction of apoptosis, assessed by morphological, flow cytometric and biochemical criteria, including proteolysis of poly(ADP-ribose) polymerase and cleavage of DNA to large kilobasepair fragments, was completely abrogated when cells were pretreated with an ICE-like protease inhibitor, Z-Val-Ala-Asp.fluoromethylketone. This suggested that an ICE homologue was a common mediator of apoptosis in THP.1 cells.
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PMID:An ICE-like protease is a common mediator of apoptosis induced by diverse stimuli in human monocytic THP.1 cells. 758 59

Substrate specificity of two collagenolytic proteases from the king crab Paralithodes camtschatica has been studied. Both proteases are shown to hydrolyze effectively type I and III collagens, gelatin and fibrinogen. The variety of products formed during the enzymatic hydrolysis of the proteins appeared to be different for crab proteases A and C. Studies on peptide hydrolysis demonstrated that protease A cleaves preferably peptide bonds with Arg and Lys as carbonyl components, while protease C prefers hydrophobic amino acids. Kinetic constants of hydrolysis for low molecular weight substrates in the presence of crab proteases have been determined. This allowed us to characterize collagenolytic protease A as a trypsin-like protease. By contrast, collagenolytic protease C was classified as chymotrypsin-like protease although this protease and bovine chymotrypsin are not completely similar. Collagenase substrates Pz-Pro-Leu-Gly-Pro-D-Arg and Z-Gly-Pro-Ala-Gly-Pro-Ala were found to be resistant to both crab proteases.
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PMID:Substrate specificity of collagenolytic proteases from the king crab Paralithodes camtschatica. 774 10

Interleukin-1 beta (IL-1 beta)-converting enzyme (ICE, caspase-1) processes the IL-1 beta precursor to mature inflammatory cytokine IL-1 beta. ICE has been identified as a unique cysteine protease, which cleaves Asp-X bonds, shows resistance to E-64 (an inhibitor of most cysteine proteases) and has a primary structure that is homologous to CED-3, a protein required for apoptosis (programmed cell death) in the nematode Caenorhabditis elegans, and to mammalian cysteine proteases that initiate and execute apoptosis, e.g., apopain/CPP32/caspase-3. The inhibitors of the ICE/CED-3 family or caspases, as they are called recently, may constitute therapeutic agents for amelioration of inflammatory and apoptosis-associated diseases. The most efficient ICE inhibitors are peptide aldehydes and peptidyl chloro or (acyloxy)methanes. A recent study revealed that both D- and L-Asp are accepted by ICE at the P1 of such inhibitors, and the peptidyl (acyloxy)methane analogues having the beta-homo-aspartyl residue [-NH-CH(CH2COOH)-CH2CO-] are inactive. These findings we reexamined in terms of two issues. (a) ICE's resistance to E-64. Since it was thought to be caused by the enzyme's unique substrate specificity, we prepared substrate-based analogues, which were not inhibitory suggesting significant structural difference between the active centers of ICE and papain-like enzymes. (b) Tolerance for D-stereochemistry at the P1 of these inhibitors. In view of the mechanism of cysteine protease inhibition by peptidyl X-methanes, we thought that this phenomenon should be a general characteristic of cysteine proteases and the hAsp-containing analogues should behave as reversible inhibitors. Here, we analyzed the inhibition of ICE and apopain in comparison with that of papain, thrombin, and trypsin by peptide L/D-alpha-aldehydes and their L-beta-homo-aldehyde [-NH-CH(R)-CH2-CHO] analogues. The following results were found. (1) The peptidyl L-beta-homo-aspartals are potent inhibitors for caspases. (2) The L-beta-homo analogues of peptide aldehyde inhibitors designed for other proteases are not inhibitory. (3) Unlike trypsin and thrombin (serine proteases), papain (cysteine protease) shows tolerance for D-stereochemistry at the P1 site of peptide aldehydes in proportion to the lability of the alpha-hydrogen of the P1-D-residue. The complete tolerance of ICE for P1-D-Asp may arise from this residue's high tendency to epimerization. (4) Reaction of cysteine proteases with peptide aldehyde or peptidyl X-methane inhibitors containing P1-D-residues may include alpha-proton abstraction followed by asymmetric induction leading to P1-L-residue-containing products.
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PMID:Peptidyl beta-homo-aspartals (3-amino-4-carboxybutyraldehydes): new specific inhibitors of caspases. 1038 Mar 58


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