THE NMR STRUCTURE OF THE INHIBITED CATALYTIC DOMAIN OF HUMAN STROMELYSIN-1

The three-dimensional structure of the catalytic domain of stromelysin -1 complexed with an N-carboxyl alkyl inhibitor has been determined by NMR methods. The global fold consists of three helices, a five strand ed beta-sheet and a methionine located in a turn near the catalytic hi stidines, classifying stromelysin-1 as a metzincin. Stromelysin-1 is u nique in having two independent zinc binding sites: a catalytic site a nd a structural site. The inhibitor binds in an extended conformation. The S1' subsite is a deep hydrophobic pocket, whereas S2' appears sha llow and 53' open.