1BQQ

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

Summary for 1BQQ

• Entry DOI: 10.2210/pdb1bqq/pdb
• Descriptor: MEMBRANE-TYPE MATRIX METALLOPROTEINASE, METALLOPROTEINASE INHIBITOR 2, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: matrix metalloproteinase, tissue inhibitor of metalloproteinases, proteinase complex, pro-gelatinase a activator, complex (metalloproteinase-receptor), hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein (Potential): P50281; Secreted: P16368
• Total number of polymer chains: 2
• Total formula weight: 40535.47

Authors

Fernandez-Catalan, C.,Bode, W.,Huber, R.,Turk, D.,Calvete, J.J.,Lichte, A.,Tschesche, H.,Maskos, K. (deposition date: 1998-08-18, release date: 1999-08-18, Last modification date: 2024-10-30)

Primary citation

Fernandez-Catalan, C.,Bode, W.,Huber, R.,Turk, D.,Calvete, J.J.,Lichte, A.,Tschesche, H.,Maskos, K.
Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor.
EMBO J., 17:5238-5248, 1998

PubMed Abstract: 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.

PubMed: 9724659
DOI: 10.1093/emboj/17.17.5238

Experimental method

X-RAY DIFFRACTION (2.75 Å)