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Biomedical subjects

J Travis

Publications and source records attributed to J Travis.

At least 271 records · Page 15Linked to original sources
PubMed1983

Human neutrophil elastase and cathepsin G cleavage sites in the bait region of alpha 2-macroglobulin. Proposed structural limits of the bait region.

The sites of cleavage in the "bait region" of human alpha 2-macroglobulin made by both neutrophil elastase and cathepsin G, as the first step in their inactivation by this inhibitor, have been identified. These positions are at a valylhistidyl bond for elastase and a phenylalanyl-tyrosyl bond for cathepsin G. All of the proteinases tested so far, including those utilized in this study, are cleaving within a twenty-seven aminoacid peptide sequence occurring between two proline residues. It is suggested that this area represents the outer limits of the "bait region" loop.

Amino Acid Sequence↗
PubMed1983

Control of coagulation and fibrinolysis by plasma proteinase inhibitors.

The control of coagulation and fibrinolytic events appears to be primarily due to four plasma proteinase inhibitors, antithrombin III, C-1-esterase inhibitor, alpha-2-antiplasmin, and alpha-2-macroglobulin. Results to date indicate that antithrombin III controls the activity of both thrombin and Factor Xa, C-1-esterase inhibitor controls kallikrein and probably activated Hageman Factor (Factor XIIa), and alpha-2-antiplasmin controls plasmin activity. The role of alpha-2-macroglobulin is not clear since it does not appear to be a primary inhibitor of any of the above enzymes. However, it is probable that it serves two functions, first as a "transfer" agent for the rapid removal of proteinases from the circulation which have been first bound by antithrombin III, C-1-esterase inhibitor, or alpha-2-antiplasmin. The second function is probably that of a back-up inhibitor when the levels of the three important controlling plasma proteins become low. The role of other plasma inhibitors such as alpha-1-proteinase inhibitor, alpha-1-antichymotrypsin, and the inter-alpha-trypsin inhibitor in coagulation and fibrinolysis would appear to be minor since these proteins either do not inactivate enzymes involved in these systems or do so at a rate too slow to be of biological significance.

Antifibrinolytic Agents↗
PubMed1982

Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases.

Human neutrophil cathepsin G and human skin mast cell chymase rapidly convert angiotensin I to angiotensin II with only minor cleavage elsewhere in the molecule. The rate of cleavage is consistent with a potential role for either or both of these enzymes in an alternate pathway for angiotensin II synthesis. Since neither enzyme in inhibited by captopril, an angiotensin converting enzyme inactivator, it is possible that leukocyte and mast cell enzymes may play a significant role in the development of abnormally high local concentrations of angiotensin II, associated with various inflammatory processes.

Amino Acids↗
PubMed1982

Complete amino acid sequence of the 4Fe-4S, thermostable ferredoxin from Clostridium thermoaceticum.

The complete amino acid sequence of the 4Fe-4S ferredoxin from the thermophilic bacterium Clostridium thermoaceticum has been determined. The protein is extremely thermostable and is the only known clostridial ferredoxin to contain a single [4Fe-4S] cluster. The sequence totals 63 residues and includes the first tryptophan (Trp-26) reported for a clostridial ferredoxin, and other amino acids not commonly found in clostridial or clostridial-like ferredoxins: methionine (Met-1), histidine (His-33), arginine (Arg-49), and leucine (Leu-9, -19, and -31). Sequence homology to clostridial and other 8Fe-8S ferredoxins is limited to eight to nine residues at the amino-terminal sulfhydryl grouping (Cys-10, -13, -16, and -20) and two to five residues in the carboxyterminal region. This ferredoxin is, thus, sequentially distinct from all known clostridial ferredoxins and from other bacterial ferredoxins in both the 8Fe-8S and 4Fe-4S classes.

Amino Acid Sequence↗
PubMed1982

The effect of alpha 2-macroglobulin on the interaction of alpha 1-proteinase inhibitor with porcine trypsin.

The rate of dissociation of the alpha 1-proteinase inhibitor:porcine trypsin complex was compared with that in the presence of alpha 2-macroglobulin. In the presence of the latter inhibitor the dissociation was more rapid and active alpha 1-proteinase inhibitor could be recovered in the mixture. However, no active inhibitor could be detected after dissociation in the absence of alpha 2-macroglobulin. This recovery of active alpha 1-proteinase inhibitor from complexes with porcine trypsin is the first demonstration of a thermodynamic equilibrium between this inhibitor and proteinase. Consequently, the transfer of trypsin from complexes with alpha 1-proteinase inhibitor to alpha 2-macroglobulin may be explained as a passive phenomenon which does not require a physical collision between alpha 2-macroglobulin and the alpha 1-proteinase inhibitor:porcine trypsin complex. The dissociation of the complex occurs more rapidly in the presence of alpha 2-macroglobulin because this inhibitor complexes trypsin leaving the alpha 1-proteinase inhibitor:porcine trypsin complex by both the irreversible breakdown step and by reversible dissociation of the complex.

Animals↗
PubMed1982

Inactivation of human plasma alpha 1-proteinase inhibitor by a metalloproteinase from Serratia marcescens.

The interaction of a Serratia marcescens metalloproteinase with human plasma alpha 1-proteinase inhibitor has been investigated. The enzyme was not inactivated by this inhibitor but, instead, converted the native plasma protein into an inactive form of decreased molecular weight. Amino terminal sequence analysis indicated that the interaction of the inhibitor and enzyme was at the reactive site of the inhibitor, with peptide-bond cleavage resulting in the inactivation. This process may be important in necrotic processes occurring during bacterial infiltration of host tissues.

Amino Acid Sequence↗
PubMed1982

Determination of oxidized alpha-1-proteinase inhibitor in serum.

When alpha-1-PI is oxidized, it loses its ability to inhibit porcine elastase, although it retains its TIC. Therefore the ratio of TIC to EIC increases in proportion to the degree of oxidation of the inhibitor. We have developed a rapid procedure for determining the percentage of oxidized alpha-1-PI in plasma or serum based on the ratio of TIC to EIC of alpha-1-PI in these tissues. The TIC/EIC ratio is not influenced by the other proteins in serum nor by the concentration of alpha-1-PI. When this technique was adapted to measure to proportion of oxidized alpha-1-PI in the serum of young adult, healthy smokers and nonsmokers, 23% oxidized inhibitor was found in the smokers' sera, whereas no oxidized alpha-1-PI was detectable in sera of nonsmokers. Thus smoking leads to oxidation damage to circulating alpha-1-PI. Reduction of the EIC of the alpha-1-PI in the serum of smokers was compensated by a 1.43-fold increase in their serum alpha-1-PI titers; however, these data do not exclude the possibility of local depletion of the absolute EIC in the extravascular space of the lungs. This assay for oxidized alpha-1-PI may be useful in studies of the relationship between oxidation of alpha-1-PI and the development of pulmonary emphysema.

Animals↗
PubMed1981

Isolation and properties of human neutrophil myeloperoxidase.

Human leukocyte myeloperoxidase has been purified to homogeneity by a three-step procedure which includes dialysis of a granule extract against low-salt buffer. Sephadex G-75 chromatography, and carboxymethylcellulose chromatography. The final product was homogeneous when examined by acid polyacrylamide gel electrophoresis and sedimentation equilibrium ultracentrifugation. The molecular weight determined by the latter procedure was 118000. With or without reduction of the protein by 2-mercaptoethanol, subunits were formed which migrated as a single band after sodium dodecyl sulfate gel electrophoresis. With reduction, the molecular weight of the apparently identical subunits was 59000, and 42000 without reduction. Other general properties of human leukocyte myeloperoxidase, including amino acid composition, amino terminal sequence analysis, and absorption spectra, are also reported. Myeloperoxidase, in the presence of hydrogen peroxide and chloride ion, and no other substrate, autoinactivates. After completion of the inactivation reaction, several oxidizable amino acids in the enzyme are modified, and the absorption peak at 430 nm disappears. The presence of a substrate of the myeloperoxidase system (alpha-1-proteinase inhibitor), or of high concentration of chloride ion, completely protects the enzyme from autoinactivation.

Amino Acid Sequence↗
PubMed1980

Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin.

The association rate constants for the interaction of alpha-1-proteinase inhibitor, oxidized alpha-1-proteinase inhibitor, and alpha-1-antichymotrypsin with several mammalian serine proteinases have been determined. The results indicate that leukocyte elastase reacts more rapidly with alpha-1-proteinase inhibitor than any other proteinase tested, while leukocyte cathepsin G shows the strongest association with alpha-1-antichymotrypsin. Oxidation of the critical methionine residue of alpha-1-proteinase inhibitor reduces the association with leukocyte elastase by a factor of more than 2000 and also lowers the association with all of the other enzymes tested with the exception of chymotrypsin. Significantly, oxidation completely abolishes any interaction of alpha-1-proteinase inhibitor with porcine elastase, human plasmin or human thrombin. These data support previous results (Johnson, D., and Travis, J. (1979) J. Biol. Chem. 254, 4022-4026) which indicated that oxidation of human alpha-1-proteinase inhibitor in vivo could reduce the effectiveness of this inhibitor in controlling proteolysis. In the lung, in particular, oxidizing agents of both chemical and biological sources could, indirectly, augment elastolysis in this tissue, resulting in the development of pulmonary emphysema.

Animals↗