PDBsum entry 1kgm

Hydrolase

PDB id: 1kgm

Contents

Protein chain

35 a.a.

References listed in PDB file

Key reference

Title

Comparative structure analysis of proteinase inhibitors from the desert locust, Schistocerca gregaria.

Authors

Z.Gáspári, A.Patthy, L.Gráf, A.Perczel.

Ref.

Eur J Biochem, 2002, 269, 527-537. [DOI no: 10.1046/j.0014-2956.2001.02685.x]

PubMed id

11856311

Abstract

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 beta-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.

Figure 3.
Fig. 3. Backbone of 10 superimposed structures of SGCI (A) and 10 superimposed structures of SGTI (B). Schematic representation of the secondary structure elements and the disulfide bonding pattern of SGCI (C) and SGTI (D). Residues giving sidechain NOEs to Phe10 in SGCI (E) and the Lys10–Trp25 interaction of SGTI (F). (A), (B), (E) and (F) were prepared with sybyl[19], (C) and (D) with molscript[38] and raster3d[39].

Figure 4.
Fig. 4. Comparison of the H -trace of the binding loop of SGCI (blue), PMP-C (red), the turkey ovomucoid third domain inhibitor [ 29 ] (green) and the Bowman-Birk inhibitor [ 30 ] (orange). Structures are superimposed between residues P3 and P3'. This figure was prepared with sybyl[19].

The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2002, 269, 527-537) copyright 2002.