1bqq

<!--The below Structure Template creates the "Structure Box" on the page. It is automatically created and periodically refreshed. All changes to the Structure Template will be lost EXCEPT for changes in the PDB parameter (setting the PDB file loaded) or the SCENE parameter (setting the initial scene to display when the page is loaded). -->

<!-- STRUCTURE TEMPLATE BEGIN -->

{{Structure

|PDB= 1bqq |SIZE=350|CAPTION= <scene name='initialview01'>1bqq</scene>, resolution 2.75&Aring;

}}

'''CRYSTAL STRUCTURE OF THE MT1-MMP--TIMP-2 COMPLEX'''

==Overview==

The proteolytic activity of matrix metalloproteinases (MMPs) towards extracellular matrix components is held in check by the tissue inhibitors of metalloproteinases (TIMPs). The binary complex of TIMP-2 and membrane-type-1 MMP (MT1-MMP) forms a cell surface located 'receptor' involved in pro-MMP-2 activation. We have solved the 2.75 A crystal structure of the complex between the catalytic domain of human MT1-MMP (cdMT1-MMP) and bovine TIMP-2. In comparison with our previously determined MMP-3-TIMP-1 complex, both proteins are considerably tilted to one another and show new features. CdMT1-MMP, apart from exhibiting the classical MMP fold, displays two large insertions remote from the active-site cleft that might be important for interaction with macromolecular substrates. The TIMP-2 polypeptide chain, as in TIMP-1, folds into a continuous wedge; the A-B edge loop is much more elongated and tilted, however, wrapping around the S-loop and the beta-sheet rim of the MT1-MMP. In addition, both C-terminal edge loops make more interactions with the target enzyme. The C-terminal acidic tail of TIMP-2 is disordered but might adopt a defined structure upon binding to pro-MMP-2; the Ser2 side-chain of TIMP-2 extends into the voluminous S1' specificity pocket of cdMT1-MMP, with its Ogamma pointing towards the carboxylate of the catalytic Glu240. The lower affinity of TIMP-1 for MT1-MMP compared with TIMP-2 might be explained by a reduced number of favourable interactions.

1BQQ is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BQQ OCA].

 

 

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Apr 7 20:42:48 2008''