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An analysis of the conformational changes that accompany the activation and inhibition of gelatinase A
Author(s) -
Crabbe Thomas,
Kelly Sharon M.,
Price Nicholas C.
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00005-1
Subject(s) - chemistry , gelatinase , biophysics , biochemistry , matrix metalloproteinase , biology
The latent precursors of the matrix metalloproteinases (MMPs) are converted by (4‐aminophenylmercuric)acetate to active forms that lose their propeptide as a result of autolysis. C.D. and an active site mutant of progelatinase A (MMP2) were used to demonstrate that, although propeptide removal is accompanied by a decrease in the enzyme's β‐sheet content, the initial activation is achieved with only minor modifications to the conformation. Mixing activated gelatinase A with the natural inhibitor, TIMP‐1, resulted in conformational changes that were absent when a synthetic inhibitor was used. The relevance of these results to MMP activation and inhibition is discussed.