CRYSTAL-STRUCTURE OF AN UNCLEAVED SERPIN REVEALS THE CONFORMATION OF AN INHIBITORY REACTIVE LOOP

The three-dimensional structure of an uncleaved serpin, a variant of h uman antichymotrypsin engineered to be an inhibitor of human neutrophi l elastase, has been determined by X-ray crystallographic methods and is currently being refined at 2.5 Angstrom resolution. It contains an intact reactive loop in a distorted helical conformation. A comparison of the current model with that of its cleaved counterpart suggests th at the conformational 'stress' of the serpin in its uncleaved and unco mplexed state may not be confined solely to the reactive loop or beta- sheet A. It is intriguing that strand s4A is not pre-inserted into bet a-sheet A of the native serpin, and this has profound implications for the mechanism of serpin function.