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

Summary 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 Sl' subsite and, consequently, small differences are observed in this subsite. Hydrogen-bond data show that, in contrast to the crystal structure, the solution structure lacks a hydrogen bond between the amide of Tyr²²³ and the carbonyl of the P3' residue. Analysis of bound water shows two tightly bound water molecules both in the solution and the crystal structure; neither of these waters are in the inhibitor binding site.Abbreviations MMP matrix metalloendoprotease - HMQC heteronuclear multiple quantum coherence - HSQC heteronuclear single quantum coherence - NOE nuclear Overhauser enhancement - NOESY NOE spectroscopy - PFG pulsed field gradient - sfSTR stromelysin-1 (EC 3.4.24.17), truncated at residue 255The coordinates of the NMR solution structure (file name 2SRT) and the X-ray crystal structure (file name 1SLN) have been deposited in the Brookhaven Protein Data Bank.