TAILIEUCHUNG - Báo cáo khoa học: Comparative structure analysis of proteinase inhibitors from the desert locust, Schistocerca gregaria

The solution structure of three small serine proteinase inhibitors, two natural and one engineered protein, SGCI (Schistocerca gregaria chymotrypsin inhibitor), SGCI[L30R, K31M] and SGTI (Schistocerca gregaria trypsin inhibitor), were determined by homonuclear NMR-spectroscopy. The molecules exhibit di erent speci®cities towards target proteinases, where SGCI is a good chymo-trypsin inhibitor, itsmutant is apotent trypsin inhibitor, and SGTI inhibits both proteinases weakly. | Eur. J. Biochem. 269 527-537 2002 FEBS 2002 Comparative structure analysis of proteinase inhibitors from the desert locust Schistocerca gregaria Zoltán Gaspari1 Andreis Patthy2 László Graf3 and Andreis Perczel1 1 Department of Organic Chemistry Eotvos L University Budapest Hungary 2Agricultural Biotechnology Center Gổdollõ Hungary 3Department of Biochemistry Eotvos L. University Budapest Hungary The solution structure of three small serine proteinase inhibitors two natural and one engineered protein SGCI Schistocerca gregaria chymotrypsin inhibitor SGCI L30R K31M and SGTI Schistocerca gregaria trypsin inhibitor were determined by homonuclear NMR-spectroscopy. The molecules exhibit different specificities towards target proteinases where SGCI is a good chymotrypsin inhibitor its mutant is a potent trypsin inhibitor and SGTI inhibits both proteinases weakly. Interestingly SGTI is a much better inhibitor of insect proteinases than of the mammalian ones used in common assays. All three molecules have a similar fold composed from three antiparallel b-pleated sheets with three disulfide bridges. The proteinase binding loop has a somewhat distinct geometry in all three peptides. Moreover the stabilization of the structure is different in SGCI and SGTI. Proton-deuterium exchange experiments are indicative of a highly rigid core in SGTI but not in SGCI. We suggest that the observed structural properties play a significant role in the specificity of these inhibitors. Keywords serine proteinase inhibitor specificity NMR structure flexibility. Despite of the enormous work dedicated to understanding the structure function and specificity of canonical serine proteinase inhibitors reviewed in 1 there are still unanswered questions awaiting detailed investigation concerning the precise mechanism of action of these molecules. All known canonical inhibitors share at least one common structural motif the proteinase binding loop although their overall fold displays no similarity in .

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