Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: CAS:61-90-5 (leucine)
60,841 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two new lethal peptides (waglerins) were purified from the venom of Trimeresurus wagleri, and sequenced. We found them to be analogs of lethal peptides (waglerins) I and II reported previously (Weinstein et al., Toxicon 29, 227-236, 1991), with an additional Ser-Leu on the amino terminus. Three of the four waglerins were synthesized and the products were chemically and biologically equivalent to the naturally occurring counterparts in venom. Murine i.p. LD50 for synthetic waglerins I, SL-I and II were 0.33, 0.22, and 0.51 mg/kg, respectively. The single, intramolecular disulfide bond in each synthetic peptide formed rapidly in high yield. The reduced (cysteine-containing) forms of the peptides appeared to have significant toxicities, even without prior disulfide bond formation, but synthetic analogs with serine substituted for cysteine were not toxic. The synthetic dimer of waglerin I, formed by two intermolecular disulfide bonds, was not toxic, but rapidly rearranged to lethal, monomeric waglerin I at alkaline pH upon the addition of 5 mM beta-mercaptoethanol. Waglerin I was inactivated by cleavage at Tyr-15 with chymotrypsin.
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PMID:Molecular properties and structure-function relationships of lethal peptides from venom of Wagler's pit viper, Trimeresurus wagleri. 144 Jun 39

Reinvestigation of the structure of the beta-chain of Hb Atlanta-Coventry (beta 75 Leu----Pro, beta 141 Leu deleted) confirmed the presence of two abnormalities; however, analysis of the aberrant beta Co14 tryptic peptide by liquid secondary ion mass spectrometry indicated that the beta 141 Leu (mass 113 daltons) was not deleted but replaced by a novel amino acid of mass 129 daltons. The new amino acid in peptide beta Co14 was uncharged at pH 6.5, more hydrophillic than leucine and susceptible to cleavage by both chymotrypsin and carboxypeptidase A. We propose that the new residue is likely to be hydroxyleucine and that it results from post-translational oxidation of beta 141 Leu as a consequence of perturbation of the haem environment caused by the beta 75 Leu----Pro mutation in the E helix (E19). This proposal is entirely consistent with recent DNA analysis which showed that beta At-Co was not the product of a third beta-globin gene and that neither of the two beta-globin genes, beta A nor beta Atlanta, contained a deletion of the beta 141 Leu codon. We have subsequently found this modified amino acid at position beta 141 in two other unstable haemoglobins, both of which involve mutations on the haem side of the E helix.
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PMID:Beta 141 Leu is not deleted in the unstable haemoglobin Atlanta-Coventry but is replaced by a novel amino acid of mass 129 daltons. 152 Jun 32

A series of analogues of chymostatin, including Z-Arg-Leu-Phe-aldehyde (Z-Arg-Leu-Phe-H), have been synthesized. Analysis of the inhibitory potential of these analogues permits identification of residues and interactions that are important for inhibitory activity. Moreover, the structure-function relationship for Z-Arg-Leu-Phe-H and chymostatin inhibition of chymotrypsin and Streptomyces griseus proteinase A (SGPA) was probed further with the aid of molecular mechanics. This analysis identified interactions that provide an explanation for the enhanced activity of the natural product, chymostatin, over the synthetic analogues in the inhibition of chymotrypsin but not SGPA.
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PMID:Synthetic analogues of chymostatin. Inhibition of chymotrypsin and Streptomyces griseus proteinase A. 153 May 79

Previously, we suggested the participation of a hemocyte proteinase in the dissociation of fat body of Sarcophaga peregrina (flesh fly) at metamorphosis. We have now purified this proteinase to near homogeneity from pupal hemocytes. It is a cysteine proteinase with a molecular mass of 29 kDa and has a unique substrate specificity hydrolyzing both Suc-Leu-Leu-Val-Tyr-MCA and Z-Phe-Arg-MCA (Suc, succinyl; MCA, methylcoumaryl-7-amide; Z, carbobenzoxy), which are substrates for chymotrypsin and cathepsin B, respectively. Partial similarity was found between the amino-terminal sequence of this proteinase and that of cathepsin B, including Pro, Glu and Arg residues conserved in the papain superfamily of enzymes.
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PMID:Purification of a 29-kDa hemocyte proteinase of Sarcophaga peregrina. 154 1

Heparan sulfate binds to proteins present on the surface of Staphylococcus aureus cells. Binding of 125I-heparan sulfate to S. aureus was time dependent, saturable, and influenced by pH and ionic strength, and cell-bound 125I-heparan sulfate was displaced by unlabelled heparan sulfate or heparin. Other glycosaminoglycans of comparable size (chondroitin sulfate and dermatan sulfate), highly glycosylated glycoprotein (hog gastric mucin), and some anionic polysaccharides (dextran sulfate and RNA) inhibited heparan sulfate binding to various extents. Heat treatment (80 degrees C for 10 min) and treatment of the bacteria with pronase E, proteinase K, pepsin, and chymotrypsin considerably reduced their ability to bind 125I-heparan sulfate, but treatment with trypsin and neuraminidase did not affect binding. Scatchard plot analysis indicated the presence of cell surface components with low affinity (Kd = 3 x 10(-5) M) for heparan sulfate. Cell surface components were released by stirring bacteria with 1 M LiCl at 37 degrees C for 2 h. Proteins of this extract that competitively inhibited binding of 125I-heparan sulfate to S. aureus were isolated by affinity chromatography on heparin-Sepharose. Two proteins having molecular masses of approximately 66 and 60 kDa and the ability to bind 125I-heparan sulfate were obtained. The first 9 amino-terminal amino acid residues of the 66-kDa protein are Asp-Trp-Thr-Gly-Trp-Leu-Ala-Ala-Ala, and the first 4 amino-terminal amino acid residues of the 60-kDa protein are Met-Leu-Val-Thr.
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PMID:Binding of heparan sulfate to Staphylococcus aureus. 154 63

An enterotoxin produced by Bacteroides fragilis was purified to homogeneity and characterized as to its biological activity and basic molecular properties. Toxin preparations were prepared by growing B. fragilis VPI 13784 in brain heart infusion broth to early stationary phase, immediately precipitating the culture supernatant fluid with 70% ammonium sulfate, and stabilizing the precipitate with the protease inhibitor TPCK (tolylsulfonyl phenylalanyl chloromethyl ketone). The toxin was sequentially purified by anion-exchange chromatography on Q-Sepharose, hydrophobic interaction chromatography on phenyl-agarose, and high-resolution ion-exchange chromatography on Mono Q. The toxin appeared homogeneous as judged by polyacrylamide gel electrophoresis. The estimated molecular weight of the highly purified toxin as determined by gel filtration chromatography on Superose-12 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis is 19,000. It has an isoelectric point of approximately 4.5 and is stable at pHs 5 to 10. The purified toxin is stable at -20 and 4 degrees C and upon freeze-drying, but it is unstable at temperatures above 55 degrees C. It is sensitive to proteinase K and Streptomyces protease but is resistant to trypsin and chymotrypsin. The activity of the purified toxin is neutralized by antiserum to a toxigenic strain of B. fragilis but not by antiserum to nontoxigenic strains. N-terminal amino acid analysis reveal an unambiguous sequence of Ala-Val-Pro-Ser-Glu-Pro-Lys-Thr-Val-Tyr-Val-Ile-Xxx-Leu-Arg-Glu-Asn-Gly- Ser-Thr . The highly purified toxin induced a strong fluid accumulation response in the lamb ileal-loop assay as well as a cytotoxic response (cell rounding) on HT-29 colon carcinoma cells. Thus, the purified toxin can cause both enterotoxic and cytotoxic activities.
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PMID:Purification and characterization of an enterotoxin from Bacteroides fragilis. 154 60

Intracutaneous injection of sarcoidosis patients with Kveim-Siltzbach antigen (KSAg), a particulate suspension of granulomatous sarcoidal spleen, induces an influx of T-helper lymphocytes and monocyte-macrophages followed by epithelioid cell granuloma formation. In the lung, similar granulomas form from an alveolitis of similar mononuclear cells, which may harbor a Kveim-like granulomagenic factor. To assess this possibility, preparations of nonviable autologous bronchoalveolar lavage cells (NABC) and KSAg were injected intracutaneously at different sites and biopsied at 4 to 5 wk. Of 22 sarcoidosis patients, nine (41%) developed typical granulomas at the NABC site, while all developed granulomas at the KSAg site. Responders to NABC had more recent onset of symptoms than nonresponders (3.2 versus 23.7 months, p less than 0.01), but did not have significantly higher percentages of lavage lymphocytes or more rosetting of lymphocytes about alveolar macrophages. None of 11 normal volunteers developed granulomas in response to NABC. Epithelioid cell granulomas at NABC and KSAg sites were similar by hematoxylin-eosin staining and by biotin-avidin-peroxidase immunohistochemical staining with monoclonal antibodies Leu-1, Leu-14, Leu-2a, Leu-3a, anti-interleukin-2 receptor, and polyclonal antibodies against lysozyme and alpha 1-anti-chymotrypsin. Symptomatic onset of sarcoidosis is associated with an autologous lavage cell factor that induces intradermal epithelioid cell granulomas that are immunophenotypically similar to Kveim-induced granulomas.
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PMID:Nonviable autologous bronchoalveolar lavage cell preparations induce intradermal epithelioid cell granulomas in sarcoidosis patients. 155 15

Exposure of rat guanidinoacetate methyltransferase to ultraviolet light in the presence of S-adenosyl-L-[methyl-3H]methionine ([methyl-3H]AdoMet) results in covalent linking of radioactivity to the enzyme protein. The incorporation of radioactivity shows no lag and is linear with respect to time up to 1 h. The photolabeling is saturable with [methyl-3H]AdoMet, and the binding constant of the enzyme for AdoMet determined in this experiment is similar to that obtained by equilibrium dialysis. Low concentrations of competitive inhibitors S-adenosyl-L-homocysteine and sinefungin effectively prevent the photoinduced labeling by AdoMet. Although guanidinoacetate methyltransferase is irreversibly inactivated upon ultraviolet irradiation in the absence of AdoMet, the enzyme inactivated by 1-h exposure to ultraviolet irradiation has been shown to bind AdoMet with an affinity identical to that of the native enzyme. These results indicate that photolabeling occurs at the active site. Following proteolysis of the [methyl-3H]-AdoMet-labeled enzyme with chymotrypsin, a radioactive peptide is isolated having a sequence Asp-Thr-X-Pro-Leu-Ser-Glu-Glu-Thr-Trp. The peptide corresponds to residues 134-143, with X being modified Tyr-136. The same peptide is photolabeled when [carboxy-14C]AdoMet is used. High-performance liquid chromatography of this peptide after acid hydrolysis and phenyl isothiocyanate derivatization suggests that the entire molecule of AdoMet is attached to Tyr-136.
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PMID:Identification of a tyrosine residue in rat guanidinoacetate methyltransferase that is photolabeled with S-adenosyl-L-methionine. 156 83

alpha-Chymotrypsin serves as a sole carbon source, sole nitrogen source, and as sole carbon plus nitrogen source for wild-type Escherichia coli in a totally defined medium. Hence, a mammalian host for E. coli may supply the necessary carbon and nitrogen nutrients for the microorganism. Growth is most rapid when chymotrypsin is a sole nitrogen source and least rapid with chymotrypsin as a carbon source. The approximate doubling times for E. coli utilizing chymotrypsin as a nitrogen source, carbon plus nitrogen source, and carbon source are 1.6, 4.6, and 11.3 h, respectively. The activity of the residual enzyme in the culture supernates falls off asymptotically over the source of time, as followed by cleavage of glutaryl-L-phenylalanine-p-nitroanilide. Chymotrypsin hydrolyzes succinyl-L-ala-L-ala-p-nitroanilide, the elastase substrate, to some extent. Peptidases do not appear to be secreted that hydrolyze such model substrates as benzoyl-DL-arginine-p-nitroanilide, the tryptic and cathepsin B substrate, L-leucine-p-nitroanilide, the leucine amino-peptidase substrate, or L-lysine-p-nitroanilide, the aminopeptidase B substrate. Growth of E. coli is generally directly related to the loss of chymotryptic activity in the medium. Hence, autolysis of chymotrypsin, i.e., self-degradation, is an important factor for the availability of degradation products of the enzyme to the bacterium for growth purposes. Accordingly, the degradation of a host protein by autolysis presents an opportunity for E. coli to survive during periods of host nutritional crisis by utilization of the degradation peptides that are produced during autolysis.
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PMID:Utilization of chymotrypsin as a sole carbon and (or) nitrogen source by Escherichia coli. 161 54

The effects of carbobenzyloxy-leucine-tyrosine-chloromethylketone (zLYCK), an inhibitor of chymotrypsin, were investigated on the activation pathways of the human neutrophil respiratory burst. At 10 microM zLYCK, a parallel inhibition was observed of superoxide production stimulated with the chemo-attractant FMLP and of chymotrypsin-like activity of human neutrophils. By contrast, superoxide production induced by PMA was minimally affected by zLYCK. The known transduction pathways triggered by FMLP were analyzed. zLYCK did not affect either the FMLP-induced cytosolic free calcium transient, inositol 1,4,5 trisphosphate formation, nor the PMA-induced phosphorylation of the 47-kDa substrate of protein kinase C. zLYCK did not affect the activity of protein kinase C extracted from neutrophils. In Ca(2+)-depleted cells, in which phosphatidylinositol 4,5-biphosphate breakdown does not occur, zLYCK inhibited the FMLP-induced respiratory burst in cells primed by low doses of PMA. The activity of the NADPH oxidase tested with active membranes from stimulated neutrophils or in a cell-free system was not inhibited by zLYCK. We conclude that: 1) zLYCK inhibits superoxide production through the inhibition of a chymotrypsin-like protease of the neutrophil, 2) zLYCK inhibits FMLP-induced activation of NADPH oxidase through a pathway independent of PtdInsP2 breakdown and cytosolic free calcium, and 3) zLYCK may prove a useful probe for the characterization of its target protease in neutrophil activation.
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PMID:The chymotrypsin inhibitor carbobenzyloxy-leucine-tyrosine-chloromethylketone interferes with the neutrophil respiratory burst mediated by a signaling pathway independent of PtdInsP2 breakdown and cytosolic free calcium. 165 5


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