|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
35
|
|
pubmed:dateCreated |
2001-8-27
|
|
pubmed:abstractText |
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.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
31
|
|
pubmed:volume |
276
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
32966-70
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:11390386-Amino Acid Sequence,
pubmed-meshheading:11390386-Amino Acid Substitution,
pubmed-meshheading:11390386-Binding Sites,
pubmed-meshheading:11390386-Crystallography, X-Ray,
pubmed-meshheading:11390386-Humans,
pubmed-meshheading:11390386-Kinetics,
pubmed-meshheading:11390386-Matrix Metalloproteinases, Membrane-Associated,
pubmed-meshheading:11390386-Metalloendopeptidases,
pubmed-meshheading:11390386-Models, Molecular,
pubmed-meshheading:11390386-Molecular Sequence Data,
pubmed-meshheading:11390386-Mutagenesis, Site-Directed,
pubmed-meshheading:11390386-Protein Conformation,
pubmed-meshheading:11390386-Protein Denaturation,
pubmed-meshheading:11390386-Protein Structure, Secondary,
pubmed-meshheading:11390386-Recombinant Proteins,
pubmed-meshheading:11390386-Sequence Alignment,
pubmed-meshheading:11390386-Sequence Deletion,
pubmed-meshheading:11390386-Sequence Homology, Amino Acid,
pubmed-meshheading:11390386-Tissue Inhibitor of Metalloproteinase-2,
pubmed-meshheading:11390386-Tyrosine
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Tyrosine 36 plays a critical role in the interaction of the AB loop of tissue inhibitor of metalloproteinases-2 with matrix metalloproteinase-14.
|
|
pubmed:affiliation |
School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, United Kingdom.
|
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|
