Remarkable phylum selectivity of a Schistocerca gregaria trypsin inhibitor

The possible role of enzyme-inhibitor flexibility

A. Patthy, Sumaira Amir, Z. Malik, Á Bódi, J. Kardos, B. Asbóth, L. Gráf

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

A 35-mer polypeptide isolated from the hemolymph of desert locust Schistocerca gregaria (SG) proved to be a canonical inhibitor of bovine trypsin (Ki = 0.2 μM). Despite having a trypsin-specific arginine at the primary specificity P1 site, it inhibits bovine chymotrypsin almost as well (Ki = 2 μM). Furthermore, while the latter reactivity improves 104-fold by the single replacement of P1 Arg by Leu, changing P1 from Lys to Met only moderately improves trypsin affinity (Ki = 30 nM). The apparent low compatibility to trypsin, however, is not observed vs two arthropodal trypsins: SG peptides with P1 Arg inhibit crayfish and shrimp trypsins with Ki values in the picomolar range. This unprecedented high discrimination between orthologous enzymes is postulated to derive from flexibility differences in the protein-protein interaction. The more than four orders of magnitude phylum selectivity makes these peptides prospective candidates for agricultural use.

Original languageEnglish (US)
Pages (from-to)179-187
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume398
Issue number2
DOIs
StatePublished - Feb 15 2002
Externally publishedYes

Fingerprint

Enzyme Inhibitors
Trypsin
Peptides
Astacoidea
Grasshoppers
Trypsin Inhibitors
Hemolymph
Chymotrypsin
Arginine
Proteins
Schistocerca gregaria SGTI protein
Enzymes

Keywords

  • Conformational flexibility
  • Endogenous inhibitors
  • FT-IR
  • Hydrogen exchange
  • Insecticides
  • Orthologous enzymes
  • Serine proteases

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Remarkable phylum selectivity of a Schistocerca gregaria trypsin inhibitor : The possible role of enzyme-inhibitor flexibility. / Patthy, A.; Amir, Sumaira; Malik, Z.; Bódi, Á; Kardos, J.; Asbóth, B.; Gráf, L.

In: Archives of Biochemistry and Biophysics, Vol. 398, No. 2, 15.02.2002, p. 179-187.

Research output: Contribution to journalArticle

@article{2cbd529decbe40e59067fc18b24f8adc,
title = "Remarkable phylum selectivity of a Schistocerca gregaria trypsin inhibitor: The possible role of enzyme-inhibitor flexibility",
abstract = "A 35-mer polypeptide isolated from the hemolymph of desert locust Schistocerca gregaria (SG) proved to be a canonical inhibitor of bovine trypsin (Ki = 0.2 μM). Despite having a trypsin-specific arginine at the primary specificity P1 site, it inhibits bovine chymotrypsin almost as well (Ki = 2 μM). Furthermore, while the latter reactivity improves 104-fold by the single replacement of P1 Arg by Leu, changing P1 from Lys to Met only moderately improves trypsin affinity (Ki = 30 nM). The apparent low compatibility to trypsin, however, is not observed vs two arthropodal trypsins: SG peptides with P1 Arg inhibit crayfish and shrimp trypsins with Ki values in the picomolar range. This unprecedented high discrimination between orthologous enzymes is postulated to derive from flexibility differences in the protein-protein interaction. The more than four orders of magnitude phylum selectivity makes these peptides prospective candidates for agricultural use.",
keywords = "Conformational flexibility, Endogenous inhibitors, FT-IR, Hydrogen exchange, Insecticides, Orthologous enzymes, Serine proteases",
author = "A. Patthy and Sumaira Amir and Z. Malik and {\'A} B{\'o}di and J. Kardos and B. Asb{\'o}th and L. Gr{\'a}f",
year = "2002",
month = "2",
day = "15",
doi = "10.1006/abbi.2001.2686",
language = "English (US)",
volume = "398",
pages = "179--187",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Remarkable phylum selectivity of a Schistocerca gregaria trypsin inhibitor

T2 - The possible role of enzyme-inhibitor flexibility

AU - Patthy, A.

AU - Amir, Sumaira

AU - Malik, Z.

AU - Bódi, Á

AU - Kardos, J.

AU - Asbóth, B.

AU - Gráf, L.

PY - 2002/2/15

Y1 - 2002/2/15

N2 - A 35-mer polypeptide isolated from the hemolymph of desert locust Schistocerca gregaria (SG) proved to be a canonical inhibitor of bovine trypsin (Ki = 0.2 μM). Despite having a trypsin-specific arginine at the primary specificity P1 site, it inhibits bovine chymotrypsin almost as well (Ki = 2 μM). Furthermore, while the latter reactivity improves 104-fold by the single replacement of P1 Arg by Leu, changing P1 from Lys to Met only moderately improves trypsin affinity (Ki = 30 nM). The apparent low compatibility to trypsin, however, is not observed vs two arthropodal trypsins: SG peptides with P1 Arg inhibit crayfish and shrimp trypsins with Ki values in the picomolar range. This unprecedented high discrimination between orthologous enzymes is postulated to derive from flexibility differences in the protein-protein interaction. The more than four orders of magnitude phylum selectivity makes these peptides prospective candidates for agricultural use.

AB - A 35-mer polypeptide isolated from the hemolymph of desert locust Schistocerca gregaria (SG) proved to be a canonical inhibitor of bovine trypsin (Ki = 0.2 μM). Despite having a trypsin-specific arginine at the primary specificity P1 site, it inhibits bovine chymotrypsin almost as well (Ki = 2 μM). Furthermore, while the latter reactivity improves 104-fold by the single replacement of P1 Arg by Leu, changing P1 from Lys to Met only moderately improves trypsin affinity (Ki = 30 nM). The apparent low compatibility to trypsin, however, is not observed vs two arthropodal trypsins: SG peptides with P1 Arg inhibit crayfish and shrimp trypsins with Ki values in the picomolar range. This unprecedented high discrimination between orthologous enzymes is postulated to derive from flexibility differences in the protein-protein interaction. The more than four orders of magnitude phylum selectivity makes these peptides prospective candidates for agricultural use.

KW - Conformational flexibility

KW - Endogenous inhibitors

KW - FT-IR

KW - Hydrogen exchange

KW - Insecticides

KW - Orthologous enzymes

KW - Serine proteases

UR - http://www.scopus.com/inward/record.url?scp=0037085228&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037085228&partnerID=8YFLogxK

U2 - 10.1006/abbi.2001.2686

DO - 10.1006/abbi.2001.2686

M3 - Article

VL - 398

SP - 179

EP - 187

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 2

ER -