Structure of the complex of leech-derived tryptase inhibitor (LDTI) with trypsin and modeling of the LDTI–tryptase system

Abstract

The insertion of nine residues after residue 174 in tryptase, relative to trypsin and chymotrypsin, prevents inhibition by other trypsin inhibitors and is certainly responsible for the higher specificity of tryptase relative to trypsin. In LDTI, the disulfide bond between residues 4 and 25 causes a sharp turn from the binding loop towards the N terminus, holding the N terminus away from the 174 loop of tryptase.

Kinetic and Thermodynamic Analysis of Leech-Derived Tryptase Inhibitor Interaction with Bovine Tryptase and Bovine Trypsin

“…The calculated curve is compatible with a simple competitive mechanism for trypsin inhibition by LDTI. This finding is in line with the crystal structure of the complex between LDTI and porcine trypsin (Di Marco and Priestle, 1997;Stubbs et al, 1997), which shows that the inhibitor binds to the active site of trypsin in a substratelike manner with residue P1 (Lys8) interacting with residue Asp 189 in the primary specificity pocket of the enzyme.…”

Molecular cloning, characterization and expression of a novel serine proteinase inhibitor gene in bay scallops (Argopecten irradians, Lamarck 1819)

“…The same result had been found in the leech-derived tryptase inhibitor [28,39], the thrombin inhibitors from T. gondii [41], D. maximus [37], R. prolixus [42], the Kazal inhibitor from crayfish blood cells [32] and the elastase inhibitor purified from whole extract of sea anemone [43]. In crayfish and sea anemone [32,43], there are six residues between cysteines 4 and 5, while in the domains of the AISPI, the leech-derived tryptase inhibitor [28,40], and the thrombin inhibitors from T. gondii [41], D. maximus [37] and R. prolixus [42], there are only two residues between Cys4 and Cys5. These differences result in a distinctive disulfide pattern, classifying this subgroup as non-classical Kazal-type inhibitors.…”

“…Six characteristic cysteine residues (C 1 eC 5 , C 2 eC 4 , C 3 eC 6 ) responsible for the formation of disulfide bridges are distributed in each of the homologous regions. The domains of AISPI are very similar to the leech-derived tryptase inhibitor [28,40], the thrombin inhibitors from Toxoplasma gondii [41], D. maximus [37] and Rhodnius prolixus [42] and so on (Fig. 2.).…”

Circular Proteins in Plants

“…The increasing incidence of discoveries of naturally occurring circular proteins coincides with the excitement currently associated with a The complexed structures were determined using x-ray crystallography with inhibitors complexed to trypsin. The Protein Data Bank accession codes are CMTI-I (solution), 2cti (31); MCTI-A, 1mct (40); CMTI-I (complexed), 1ppe (41); CPTI-II, 2btc (42); SFTI-I, 1sfi (17); LDTI, 1anl (43) . FIG.…”