COMPARISON OF THE STRUCTURE OF HUMAN RECOMBINANT SHORT-FORM STROMELYSIN BY MULTIDIMENSIONAL HETERONUCLEAR NMR AND X-RAY CRYSTALLOGRAPHY

Stromelysin-1 is a matrix metalloprotease that has been implicated in a number of degenerative diseases. Here we present the refined NMR sol ution structure of the catalytic domain of stromelysin-1 complexed wit h a small inhibitor and compare it to the X-ray crystal structure of t he same complex. The structures are similar in global fold and show an unusual bottomless S1' subsite. There are differences, however, in th e least well defined regions, Phe(83)-Ile(89), His(224)-Phe(232) and p ro(249)-pro(250), reflecting the lack of NOE data and large B-factors. The region His(224)-Phe(232) contains residues of the S1' subsite and , consequently, small differences are observed in this subsite. Hydrog en-bond data show that, in contrast to the crystal structure, the solu tion structure lacks a hydrogen bond between the amide of Ty(223) and the carbonyl of the P3' residue. Analysis of bound water shows two tig htly bound water molecules both in the solution and the crystal struct ure; neither of these waters are in the inhibitor binding site.