X-ray structure of a novel matrix metalloproteinase inhibitor complexed tostromelysin

Citation
P. Dunten et al., X-ray structure of a novel matrix metalloproteinase inhibitor complexed tostromelysin, PROTEIN SCI, 10(5), 2001, pp. 923-926
Citations number
17
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEIN SCIENCE
ISSN journal
0961-8368 → ACNP
Volume
10
Issue
5
Year of publication
2001
Pages
923 - 926
Database
ISI
SICI code
0961-8368(200105)10:5<923:XSOANM>2.0.ZU;2-3
Abstract
A new class of matrix metalloproteinase (MMP) inhibitors has been identifie d by screening a collection of compounds against stromelysin. The inhibitor s, 2,4,6-pyrimidine triones, have proven to be potent inhibitors of gelatin ases A and B. An X-ray crystal structure of one representative compound bou nd to the catalytic domain of stromelysin shows that the compounds bind at the active site and Ligand the active-site zinc. The pyrimidine triones mim ic substrates in forming hydrogen bonds to key residues in the active site, and provide opportunities for placing appropriately chosen groups into the S1' specificity pocket of MMPs. A number of compounds have been synthesize d and assayed against stromelysin, and the variations in potency are explai ned in terms of the binding mode revealed in the X-ray crystal structure.