Squash inhibitor family of serine proteinases.
Squash inhibitors of serine proteinases form an uniform family of small proteins. They are built of 27-33 amino-acid residues and cross-linked with three disulfide bridges. The reactive site peptide bond (P1-P1') is between residue 5 (Lys, Arg or Leu) and 6 (always Ile). High resolution X-ray structures are available for two squash inhibitors complexed with trypsin. NMR solution structures have also been determined for free inhibitors. The major structural motif is a distorted, triple-stranded antiparallel beta-sheet. A similar folding motif has been recently found in a number of proteins, including: conotoxins from fish-hunting snails, carboxypeptidase inhibitor from potato, kalata B1 polypeptide, and in some growth factors (e.g. nerve growth factor, transforming growth factor beta 2, platelet-derived growth factor). Squash inhibitors are highly stable and rigid proteins. They inhibit a number of serine proteinases: trypsin, plasmin, kallikrein, blood clotting factors: Xa and XIIa, cathepsin G. The inhibition spectrum can be much broadened if specific amino-acid substitutions are introduced, especially at residues which contact proteinase. Squash inhibitors inhibit proteinases via the standard mechanism. According to the mechanism, inhibitors are substrates which exibit at neutral pH a high kcat/K(m) index for hydrolysis and resynthesis of the reactive site, and a low value of the hydrolysis constant.
Otlewski
J
J
Institute of Biochemistry, University of Wrocław, Poland. otlewski@ii.uni.wroc.pl
Krowarsch
D
D
D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry; D006868:Hydrolysis; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D014362:Trypsinogen / Q000737:chemistry; D014675:Vegetables / Q000737:chemistry*
D004220:Disulfides; D015842:Serine Proteinase Inhibitors; D014362:Trypsinogen