Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor
- 1 February 1994
- journal article
- Published by Springer Nature in Nature Structural & Molecular Biology
- Vol. 1 (2) , 106-110
- https://doi.org/10.1038/nsb0294-106
Abstract
In rheumatoid and osteoarthritis, degradation of articular cartilage is mediated by the matrix metalloproteinases collagenase, stromelysin and gelatinase. The key event in this process is the cleavage of triple helical collagen by collagenase. We have determined the crystal structure of the catalytic domain of human recombinant fibroblast collagenase complexed with a synthetic inhibitor at 2.2 A resolution. The protein fold is similar to the amino termini of the zinc endopeptidases astacin thermolysin and elastase despite a lack of primary sequence homology. The conformation of the bound inhibitor provides a molecular basis for the design of inhibitors of collagenase and other matrix metalloproteinases. Such inhibitors should be useful in the treatment of a variety of diseases including arthritis and cancer.Keywords
This publication has 26 references indexed in Scilit:
- The Recombinant Catalytic Domain of Human Neutrophil Collagenase Lacks Type I Collagen Substrate SpecificityBiochemical and Biophysical Research Communications, 1993
- The matrix metalloproteinases and their natural inhibitors: prospects for treating degenerative tissue diseasesTrends in Biotechnology, 1992
- Structure of astacin and implications for activation of astacins and zinc-ligation of collagenasesNature, 1992
- Metal ion stabilization of the conformation of a recombinant 19‐kDa catalytic fragment of human fibroblast collagenaseProteins-Structure Function and Bioinformatics, 1992
- Antibodies to Proteus in Rheumatoid ArthritisRheumatology, 1991
- The origin of matrix metalloproteinases and their familial relationshipsFEBS Letters, 1991
- An internal cysteine plays a role in the maintenance of the latency of human fibroblast collagenaseBiochemistry, 1991
- Role and regulation of metalloproteinases in connective tissue turnoverBiochemical Society Transactions, 1990
- Fragments of human fibroblast collagenase. Purification and characterizationBiochemical Journal, 1989
- Collagenase Inhibitors: Their Design and Potential Therapeutic UseJournal of Enzyme Inhibition, 1987