Abstract
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 beta-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.
MeSH terms
-
Amino Acid Sequence
-
Circular Dichroism
-
Enzyme Activation / drug effects
-
Gelatinases / antagonists & inhibitors*
-
Gelatinases / chemistry*
-
Gelatinases / metabolism
-
Glycoproteins / pharmacology
-
Humans
-
Matrix Metalloproteinase 2
-
Metalloendopeptidases / antagonists & inhibitors*
-
Metalloendopeptidases / chemistry*
-
Metalloendopeptidases / metabolism
-
Molecular Sequence Data
-
Molecular Weight
-
Mutation
-
Phenylmercuric Acetate / analogs & derivatives
-
Phenylmercuric Acetate / pharmacology
-
Protease Inhibitors / pharmacology
-
Protein Conformation
-
Protein Precursors / chemistry
-
Tissue Inhibitor of Metalloproteinases
Substances
-
Glycoproteins
-
Protease Inhibitors
-
Protein Precursors
-
Tissue Inhibitor of Metalloproteinases
-
4-aminophenylmercuriacetate
-
Gelatinases
-
Metalloendopeptidases
-
Matrix Metalloproteinase 2
-
Phenylmercuric Acetate