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Tyrosine 36 plays a critical role in the interaction of the AB loop of tissue inhibitor of metalloproteinases-2 with matrix metalloproteinase-14.

Williamson, Richard A., Hutton, Mike, Vogt, Gavin, Rapti, Magdalene, Knauper, Vera, Carr, Mark D., Murphy, Gillian (2001) Tyrosine 36 plays a critical role in the interaction of the AB loop of tissue inhibitor of metalloproteinases-2 with matrix metalloproteinase-14. Journal of Biological Chemistry, 276 . pp. 32966-32970. ISSN 0021-9258. E-ISSN 1083-351X. (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:75)

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Abstract

The tissue inhibitor of metalloproteinases-2 (TIMP-2) is potentially an important inhibitor of all known matrix metalloproteinases (MMPs). However, it has been shown to undergo specific interactions with both MMP-2 (gelatinase A) and MMP-14 (MT1-MMP), and it has been proposed that these three proteins function as a cell surface-based activation cascade for matrix metalloproteinases and as a focus of proteolytic activity. In this study, we have carried out mutagenesis and kinetic analyses to examine the unique interactions between the AB loop of TIMP-2 and MMP-14. The results demonstrate that the major binding contribution of the AB loop is due solely to residue Tyr-36 at the tip of the hairpin. From this work, we propose that TIMP-2 may be engineered to abrogate MMP-14 binding, whereas its binding properties for other MMPs, including MMP-2, are maintained. Mutants of TIMP-2 with more directed specificity may be of use in gene therapeutic approaches to human disease.

Item Type: Article
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Susan Davies
Date Deposited: 19 Dec 2007 17:54 UTC
Last Modified: 05 Nov 2024 09:29 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/75 (The current URI for this page, for reference purposes)

University of Kent Author Information

Williamson, Richard A..

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