The effect of matrix metalloproteinase complex formation on the conformational mobility of tissue inhibitor of metalloproteinases-2 (TIMP-2)

Williamson, R.A. and Muskett, F.W. and Howard, M.J. and Freedman, R.B. and Carr, M.D. (1999) The effect of matrix metalloproteinase complex formation on the conformational mobility of tissue inhibitor of metalloproteinases-2 (TIMP-2). Journal of Biological Chemistry, 274 (52). pp. 37226-37232. ISSN 0021-9258. (The full text of this publication is not available from this repository)

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Abstract

The backbone mobility of the N-terminal domain of tissue inhibitor of metalloproteinases-2 (N-TIMP-2) was determined both for the free protein and when bound to the catalytic domain of matrix metalloproteinase-3 (N-MMP-3). Regions of the protein with internal motion were identified by comparison of the T(1) and T(2) relaxation times and (1)H-(15)N nuclear Overhauser effect values for the backbone amide (15)N signals for each residue in the sequence. This analysis revealed rapid internal motion on the picosecond to nanosecond time scale for several regions of free N-TIMP-2, including the extended beta-hairpin between beta-strands A and B, which forms part of the MMP binding site. Evidence of relatively slow motion indicative of exchange between two or more local conformations on a microsecond to millisecond time scale was also found in the free protein, including two other regions of the MMP binding site (the CD and EF loops). On formation of a tight N-TIMP-2. N-MMP-3 complex, the rapid internal motion of the AB beta-hairpin was largely abolished, a change consistent with tight binding of this region to the MMP-3 catalytic domain. The extended AB beta-hairpin is not a feature of all members of the TIMP family; therefore, the binding of this highly mobile region to a site distant from the catalytic cleft of the MMPs suggests a key role in TIMP-2 binding specificity.

Item Type: Article
Additional information: 0021-9258 (Print) Journal Article Research Support, Non-U.S. Gov't
Uncontrolled keywords: Amino Acid Sequence Binding Sites Catalytic Domain Humans Matrix Metalloproteinase 3/*chemistry/metabolism Molecular Sequence Data Protein Conformation Tissue Inhibitor of Metalloproteinase-2/*chemistry/metabolism
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences > Protein Science Group
Depositing User: Richard Williamson
Date Deposited: 16 Mar 2009 15:39
Last Modified: 14 Jan 2010 14:20
Resource URI: http://kar.kent.ac.uk/id/eprint/5323 (The current URI for this page, for reference purposes)
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