STRUCTURE OF LEECH DERIVED TRYPTASE INHIBITOR (LDTI-C) IN SOLUTION

The three-dimensional solution structure of the leech derived tryptase inhibitor form C(LDTI-C), an inhibitor of 46 amino acids which contai ns 3 disulfide bridges, has been determined using 2D NMR spectroscopy. The 3D structure was determined on the basis of 262 interresidue inte rproton distance constraints derived from nuclear Overhauser enhanceme nt measurements and 25 phi angles, supplemented by 3 phi, and 15(chi 1 ), angles. The core of LDTI-C is very well defined and consists of a s hort 3(10)sigma-helix-loop and a short two-stranded antiparallel beta- 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 t he beta-sheet via the third disulfide bridge. The binding loop in LDTI exhibits lowest energy conformations belonging to the canonical confo rmation of serine proteinase inhibitors.