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 language | English (US) |
|---|---|
| Pages (from-to) | 179-187 |
| Number of pages | 9 |
| Journal | Archives of Biochemistry and Biophysics |
| Volume | 398 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 15 2002 |
| Externally published | Yes |
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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 journal › Article
}
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
C2 - 11831848
AN - SCOPUS:0037085228
VL - 398
SP - 179
EP - 187
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
IS - 2
ER -