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PMID: 1317162 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The C-terminal domain of 72 kDa gelatinase A is not required for catalysis, but is essential for membrane activation and modulates interactions with tissue inhibitors of metalloproteinases.

The Biochemical journal ·Vol. 283 ( Pt 3) ·1992-05-01 ·Pages 637-41

Murphy G, Willenbrock F, Ward RV, Cockett MI, Eaton D, Docherty AJ

Abstract

Recombinant 72 kDa gelatinase A and a truncated form lacking the C-terminal domain were shown to be activated by organomercurials and to possess similar activities towards a number of substrates. The truncated proenzyme differed from the full-length gelatinase in that it could not be activated by a membrane activator and did not bind tissue inhibitor of metalloproteinase (TIMP)-2. Kinetic studies also showed that the inhibition of the activated truncated enzyme, by both TIMP-1 and TIMP-2, was considerably decreased compared with the full-length enzyme. We conclude that the C-terminal domain plays an important role in the regulation of gelatinase A by a potential physiological activator and inhibitors.

MeSH Terms
Base Sequence Catalysis Cell Membrane/enzymology DNA/chemistry Enzyme Activation Gelatinases Glycoproteins/metabolism,pharmacology Humans Kinetics Molecular Sequence Data Molecular Weight Mutagenesis Neoplasm Proteins/metabolism,pharmacology Pepsin A/chemistry,genetics,metabolism Peptide Fragments/metabolism Structure-Activity Relationship Tissue Inhibitor of Metalloproteinase-2 Tissue Inhibitor of Metalloproteinases
Chemicals
Glycoproteins Neoplasm Proteins Peptide Fragments Tissue Inhibitor of Metalloproteinases Tissue Inhibitor of Metalloproteinase-2 DNA Pepsin A Gelatinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Murphy G
Strangeways Research Laboratory, Worts Causeway, Cambridge, U.K.
Willenbrock F
Ward R V
Cockett M I
Eaton D
Docherty A J
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2830637
Published
1992-05-01
Pages
637-41
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1130931
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1042/bj2830637 PMC Full Text View journal details
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