RECOMBINANT APROTININ HOMOLOG WITH NEW INHIBITORY SPECIFICITY FOR CATHEPSIN-G

BRINKMANN T, SCHNIERER S, Tschesche H (1991)
EUROPEAN JOURNAL OF BIOCHEMISTRY 202(1): 95-99.

Journal Article | Published | English

No fulltext has been uploaded

Author
; ;
Abstract
The substitution of amino acids in the reactive site of aprotinin, a bovine serine proteinase inhibitor with potent activity against trypsin, plasmin and tissue kallikrein, led to a change in specificity of the inhibitor. Twelve new aprotinin variants prepared by recombinant DNA technology and expressed in Escherichia coli clearly demonstrated that the neighbouring groups of the P1 residue, in particular P'2, contribute to the specificity of the inhibitor, while earlier investigations on semisynthetically prepared variants revealed the importance of the P1 residue in dominating the inhibitory specificity. Recombinant aprotinin variants which act specifically against chymotrypsin-like proteinases, were obtained by substitution of the amino acids in position P1 and P'2 by hydrophobic amino acids like phenylalanine, tyrosine and leucine. Some of these variants, particularly those with phenylalanine or leucine substitutions, were also found to exhibit inhibitory activity against cathepsin G with an equilibrium constant of dissociation K(i) of 10(-8) M. Inhibitory specificity against cathepsin G was not found in any semisynthetic variant prepared earlier.
Publishing Year
ISSN
eISSN
PUB-ID

Cite this

BRINKMANN T, SCHNIERER S, Tschesche H. RECOMBINANT APROTININ HOMOLOG WITH NEW INHIBITORY SPECIFICITY FOR CATHEPSIN-G. EUROPEAN JOURNAL OF BIOCHEMISTRY. 1991;202(1):95-99.
BRINKMANN, T., SCHNIERER, S., & Tschesche, H. (1991). RECOMBINANT APROTININ HOMOLOG WITH NEW INHIBITORY SPECIFICITY FOR CATHEPSIN-G. EUROPEAN JOURNAL OF BIOCHEMISTRY, 202(1), 95-99.
BRINKMANN, T., SCHNIERER, S., and Tschesche, H. (1991). RECOMBINANT APROTININ HOMOLOG WITH NEW INHIBITORY SPECIFICITY FOR CATHEPSIN-G. EUROPEAN JOURNAL OF BIOCHEMISTRY 202, 95-99.
BRINKMANN, T., SCHNIERER, S., & Tschesche, H., 1991. RECOMBINANT APROTININ HOMOLOG WITH NEW INHIBITORY SPECIFICITY FOR CATHEPSIN-G. EUROPEAN JOURNAL OF BIOCHEMISTRY, 202(1), p 95-99.
T. BRINKMANN, S. SCHNIERER, and H. Tschesche, “RECOMBINANT APROTININ HOMOLOG WITH NEW INHIBITORY SPECIFICITY FOR CATHEPSIN-G”, EUROPEAN JOURNAL OF BIOCHEMISTRY, vol. 202, 1991, pp. 95-99.
BRINKMANN, T., SCHNIERER, S., Tschesche, H.: RECOMBINANT APROTININ HOMOLOG WITH NEW INHIBITORY SPECIFICITY FOR CATHEPSIN-G. EUROPEAN JOURNAL OF BIOCHEMISTRY. 202, 95-99 (1991).
BRINKMANN, T, SCHNIERER, S, and Tschesche, Harald. “RECOMBINANT APROTININ HOMOLOG WITH NEW INHIBITORY SPECIFICITY FOR CATHEPSIN-G”. EUROPEAN JOURNAL OF BIOCHEMISTRY 202.1 (1991): 95-99.
This data publication is cited in the following publications:
This publication cites the following data publications:

7 Citations in Europe PMC

Data provided by Europe PubMed Central.

Inactivation of ADAMTS13 by plasmin as a potential cause of thrombotic thrombocytopenic purpura.
Feys HB, Vandeputte N, Palla R, Peyvandi F, Peerlinck K, Deckmyn H, Lijnen HR, Vanhoorelbeke K., J. Thromb. Haemost. 8(9), 2010
PMID: 20553378
Specificity of human cathepsin G.
Polanowska J, Krokoszynska I, Czapinska H, Watorek W, Dadlez M, Otlewski J., Biochim. Biophys. Acta 1386(1), 1998
PMID: 9675278
The 1.8 A crystal structure of human cathepsin G in complex with Suc-Val-Pro-PheP-(OPh)2: a Janus-faced proteinase with two opposite specificities.
Hof P, Mayr I, Huber R, Korzus E, Potempa J, Travis J, Powers JC, Bode W., EMBO J. 15(20), 1996
PMID: 8896442
Plasmodium chabaudi p68 serine protease activity required for merozoite entry into mouse erythrocytes.
Breton CB, Blisnick T, Jouin H, Barale JC, Rabilloud T, Langsley G, Pereira da Silva LH., Proc. Natl. Acad. Sci. U.S.A. 89(20), 1992
PMID: 1409678

23 References

Data provided by Europe PubMed Central.

Expression, isolation and characterization of recombinant [Arg15,Glu52]aprotinin.
Auerswald EA, Horlein D, Reinhardt G, Schroder W, Schnabel E., Biol. Chem. Hoppe-Seyler 369 Suppl(), 1988
PMID: 2462433

Mannheim, 1989

Brinkmann, Biol. Chem. Hoppe-Seyler 371 Suppl (), 1990

Creighton, J. Biol. Chem 39(), 1986

AUTHOR UNKNOWN, 0

Fritz, Arzneim.-Forsch 33(), 1983
Pancreatic trypsin inhibitor. II. Reaction with trypsin.
GREEN NM, WORK E., Biochem. J. 54(2), 1953
PMID: 13058883
Enzymatic semisynthesis of aprotinin homologues mutated in P' positions.
Groeger C, Wenzel HR, Tschesche H., J. Protein Chem. 10(2), 1991
PMID: 1718310
The basic trypsin inhibitor of bovine pancreas. I. Structure analysis and conformation of the polypeptide chain.
Huber R, Kukla D, Ruhlmann A, Epp O, Formanek H., Naturwissenschaften 57(8), 1970
PMID: 5447861

Maniatis, 1982
DNA sequencing with chain-terminating inhibitors.
Sanger F, Nicklen S, Coulson AR., Proc. Natl. Acad. Sci. U.S.A. 74(12), 1977
PMID: 271968

AUTHOR UNKNOWN, 0
On the size of the active site in proteases. I. Papain.
Schechter I, Berger A., Biochem. Biophys. Res. Commun. 27(2), 1967
PMID: 6035483

AUTHOR UNKNOWN, 0
Human leukocyte cathepsin G. Subsite mapping with 4-nitroanilides, chemical modification, and effect of possible cofactors.
Tanaka T, Minematsu Y, Reilly CF, Travis J, Powers JC., Biochemistry 24(8), 1985
PMID: 4016099

AUTHOR UNKNOWN, 0

Tschesche, Angew. Chem 86(), 1974
Biochemistry of natural proteinase inhibitors.
Tschesche H., Angew. Chem. Int. Ed. Engl. 13(1), 1974
PMID: 4205687
Semisynthetic engineering of proteinase inhibitor homologues.
Tschesche H, Beckmann J, Mehlich A, Schnabel E, Truscheit E, Wenzel HR., Biochim. Biophys. Acta 913(1), 1987
PMID: 2437960

Wenzel, Angew. Chem 93(), 1981

Export

0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®

Sources

PMID: 1718753
PubMed | Europe PMC

Search this title in

Google Scholar