SOLUTION STRUCTURE OF R-ELAFIN, A SPECIFIC INHIBITOR OF ELASTASE

The solution structure of r-elafin, a specific elastase inhibitor, has been determined using NMR spectroscopy. Characterized by a flat core and a flexible N-terminal extremity, the three-dimensional structure i s formed by a central twisted beta-hairpin accompanied by two external segments linked by the proteinase binding loop. A cluster of three di sulfide bridges connects the external segments to the central beta-she et and a single fourth disulfide bridge links the binding loop to the central beta-turn. The same spatial distribution of disulfide bridges can be observed in both domains of the secretory leukocyte protease in hibitor (SLPI), another elastase inhibitor. The structural homology be tween r-elafin and the C-terminal domain of SLPI confirms the former a s a second member of the chelonianin family of proteinase inhibitors. Based on the homology between the two proteins and recent results obta ined for elastase binding mutants of the bovine pancreatic trypsin inh ibitor (BPTI), we define the segment 22 to 27 as the binding loop of e lafin, with the scissile peptide bond between Ala24 and Met25. In our solution structures, this loop is extended and solvent-exposed, and ex hibits a large degree of flexibility. This mobility, already observed for the binding loop in other protease inhibitors in solution, might b e an important feature for the interaction with the corresponding prot ease. (C) 1997 Academic Press Limited.