Structure of leech derived tryptase inhibitor (LDTI‐C) in solution

Abstract

The three-dimensional solution structure of the leech derived tryptase inhibitor form C (LDTI-C), an inhibitor of 46 amino acids which contains 3 disulfide bridges, has been determined using 2D NMR spectroscopy. The 3D structure was determined on the basis of 262 interresidue interproton distance constraints derived from nuclear Overhauser enhancement measurements and 25 φ angles, supplemented by 3 ϕ and 15_χ1 angles. The core of LDTI-C is very well defined and consists of a short 3₁₀-helix-loop and a short two-stranded antiparallel β-sheet between residues 13–14 and 20–21. The N-terminus is fixed to the core by two disulfide bridges, while the C-terminus is connected to the β-sheet via the third disulfide bridge. The binding loop in LDTI exhibits lowest energy conformations belonging to the canonical conformation of serine proteinase inhibitors.