Inhibition of tryptase TL2 from human T4(+) lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues

Brinkmann T, Schafers J, Gurtler L, Kido H, Niwa Y, Katunuma N, Tschesche H (1997)
JOURNAL OF PROTEIN CHEMISTRY 16(6): 651-660.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
The serine esterase TL2 from human T4(+) lymphocytes is a binding component to HIV-1 glycoprotein gp120 and seems to play a role in the HIV-1 infection mechanism. Recombinant variants of the Kunitz-type serine proteinase inhibitor aprotinin were investigated for their ability to inhibit tryptase TL2 and the binding of gp120 to this enzyme, Furthermore, the viral replication of HIV-1 was investigated in H9 cell cultures under the influence of recombinant aprotinin and bikunin variants. In contrast to native aprotinin, the recombinant variant [Arg(15), Phe(17), Glu(52)]aprotinin with a reactive-site sequence homologous to the V3 loop of HIV-1 gp120 showed a specific inhibition of tryptase TL2 (>80%). However, the [Leu(15), Phe(17), Glu(52)]aprotinin variant with hydrophobic subsites was the most potent inhibitor of the binding of gp120 to tryptase TL2 (68%). Our results show that the enzyme activity of purified tryptase TL2 is inhibited not only by variants with basic amino acids, but also those with hydrophobic residues in the reactive-site region. Therefore, tryptase TH2 is not a typical trypsin-like or chymotrypsin-like protease, Investigations on inhibition of HIV-1 replication in H9 cell cultures showed that tryptase TL2 is involved in the mechanism of virus internalization into human lymphocytes. The [Leu(15), Phe(17), Glu(52)]aprotinin showed a significant retardation of syncytium formation over a period of 5 days in a 1 mu M concentration. Similar investigations were performed with recombinant variants of bikunin, the light chain of human inter-alpha-trypsin inhibitor, Only the single-headed variant [Arg(94)](delta 2) bikunin inhibited slightly the syncytium formation over a period of 2 days in a 2.2 mu M concentration, Wild-type bikunin and all full-length variants showed no effect, possibly due to steric hindrance by the second domain of the double-headed inhibitor.
Stichworte
Kunitz-type inhibitor; bikunin; tryptase TL2; HIV infection; aprotinin
Erscheinungsjahr
1997
Zeitschriftentitel
JOURNAL OF PROTEIN CHEMISTRY
Band
16
Ausgabe
6
Seite(n)
651-660
ISSN
0277-8033
Page URI
https://pub.uni-bielefeld.de/record/1627726

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Brinkmann T, Schafers J, Gurtler L, et al. Inhibition of tryptase TL2 from human T4(+) lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues. JOURNAL OF PROTEIN CHEMISTRY. 1997;16(6):651-660.
Brinkmann, T., Schafers, J., Gurtler, L., Kido, H., Niwa, Y., Katunuma, N., & Tschesche, H. (1997). Inhibition of tryptase TL2 from human T4(+) lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues. JOURNAL OF PROTEIN CHEMISTRY, 16(6), 651-660. doi:10.1023/A:1026379109403
Brinkmann, T., Schafers, J., Gurtler, L., Kido, H., Niwa, Y., Katunuma, N., and Tschesche, H. (1997). Inhibition of tryptase TL2 from human T4(+) lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues. JOURNAL OF PROTEIN CHEMISTRY 16, 651-660.
Brinkmann, T., et al., 1997. Inhibition of tryptase TL2 from human T4(+) lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues. JOURNAL OF PROTEIN CHEMISTRY, 16(6), p 651-660.
T. Brinkmann, et al., “Inhibition of tryptase TL2 from human T4(+) lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues”, JOURNAL OF PROTEIN CHEMISTRY, vol. 16, 1997, pp. 651-660.
Brinkmann, T., Schafers, J., Gurtler, L., Kido, H., Niwa, Y., Katunuma, N., Tschesche, H.: Inhibition of tryptase TL2 from human T4(+) lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues. JOURNAL OF PROTEIN CHEMISTRY. 16, 651-660 (1997).
Brinkmann, T, Schafers, J, Gurtler, L, Kido, H, Niwa, Y, Katunuma, N, and Tschesche, Harald. “Inhibition of tryptase TL2 from human T4(+) lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues”. JOURNAL OF PROTEIN CHEMISTRY 16.6 (1997): 651-660.

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