NTR

Tissue inhibitor of metalloproteinase family.
NTR
SMART accession number:SM00206
Description: Form complexes with metalloproteinases, such as collagenases, and irreversibly inactivate them.
Interpro abstract (IPR001820):

Tissue inhibitors of metalloproteinases (TIMPs, [ (PUBMED:2793861) (PUBMED:1850705) (PUBMED:1512267) ]) and their target matrix metalloproteinases (MMPs, MEROPS peptidase family M10A) are important in connective tissue re-modelling in diseases of the cardiovascular system and in the physiological degradation of connective tissue, as well as in pathological states such as tumour invasion and arthritis. TIMPs belong to MEROPS proteinase inhibitor family I35, clan IT.

TIMPs complex with extracellular matrix metalloproteinases (such as collagenases) and irreversibly inactivate them. Members of this family are common in extracellular regions of vertebrate species [ (PUBMED:7918391) ]. TIMPs are proteins of about 200 amino acid residues, 12 of which are cysteines involved in disulphide bonds [ (PUBMED:2163605) ]. The basic structure of such a type of inhibitor is shown in the following schematic representation:


+-----------------------------+ +--------------+
| | | |
CxCxCxxxxxxxxxxxxxxxxxCxxxxxxxxxCxxxxxxxCxCxCxCxCxxxxxCxxCxxx
| | | | | | | |
| +-----------------|-----------------+ +-+ +-----+
+---------------------+

'C': conserved cysteine involved in a disulphide bond.

The crystal structure of the human proMMP-2/TIMP-2 complex reveals an interaction between the hemopexin domain of proMMP-2 and the C-terminal domain of TIMP-2, leaving the catalytic site of MMP-2 and the inhibitory site of TIMP-2 distant and spatially isolated. The interfacial contact of these two proteins is characterised by two distinct binding regions composed of alternating hydrophobic and hydrophilic interactions. This unique structure provides information for how specificity for non-inhibitory MMP/TIMP complex formation is achieved [ (PUBMED:12032297) ].

GO function:metalloendopeptidase inhibitor activity (GO:0008191)
Family alignment:
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There are 1422 NTR domains in 1421 proteins in SMART's nrdb database.

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