Comparison of the structure of human recombinant short form stromelysin by multidimensional heteronuclear NMR and X-ray crystallography

Abstract

Stromelysin-1 is a matrix metalloprotease that has been implicated in a number of degenerative diseases. Here we present the refined NMR solution structure of the catalytic domain of stromelysin-1 complexed with a small inhibitor and compare it to the X-ray crystal structure of the same complex. The structures are similar in global fold and show an unusual bottomless S1′ subsite. There are differences, however, in the least well defined regions, Phe83-Ile89, His224-Phe232 and Pro249-Pro250, reflecting the lack of NOE data and large B-factors. The region His224-Phe232 contains residues of the S1′ subsite and, consequently, small differences are observed in this subsite. Hydrogen-bond data sho..