1HOV

SOLUTION STRUCTURE OF A CATALYTIC DOMAIN OF MMP-2 COMPLEXED WITH SC-74020

Summary for 1HOV

• Entry DOI: 10.2210/pdb1hov/pdb
• Descriptor: MATRIX METALLOPROTEINASE-2, ZINC ION, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: enzyme-inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix: P08253
• Total number of polymer chains: 1
• Total formula weight: 19277.10

Authors

Feng, Y.,Likos, J.J.,Zhu, L.,Woodward, H.,Munie, G.,McDonald, J.J.,Stevens, A.M.,Howard, C.P.,De Crescenzo, G.A.,Welsch, D.,Shieh, H.-S.,Stallings, W.C. (deposition date: 2000-12-11, release date: 2001-12-12, Last modification date: 2024-05-22)

Primary citation

Feng, Y.,Likos, J.J.,Zhu, L.,Woodward, H.,Munie, G.,McDonald, J.J.,Stevens, A.M.,Howard, C.P.,De Crescenzo, G.A.,Welsch, D.,Shieh, H.-S.,Stallings, W.C.
Solution structure and backbone dynamics of the catalytic domain of matrix metalloproteinase-2 complexed with a hydroxamic acid inhibitor
Biochim.Biophys.Acta, 1598:10-23, 2002

PubMed Abstract: MMP-2 is a member of the matrix metalloproteinase family that has been implicated in tumor cell metastasis and angiogenesis. Here, we describe the solution structure of a catalytic domain of MMP-2 complexed with a hydroxamic acid inhibitor (SC-74020), determined by three-dimensional heteronuclear NMR spectroscopy. The catalytic domain, designated MMP-2C, has a short peptide linker replacing the internal fibronectin-domain insertion and is enzymatically active. Distance geometry-simulated annealing calculations yielded 14 converged structures with atomic root-mean-square deviations (r.m.s.d.) of 1.02 and 1.62 A from the mean coordinate positions for the backbone and for all heavy atoms, respectively, when 11 residues at the N-terminus are excluded. The structure has the same global fold as observed for other MMP catalytic domains and is similar to previously solved crystal structures of MMP-2. Differences observed between the solution and the crystal structures, near the bottom of the S1' specificity loop, appear to be induced by the large inhibitor present in the solution structure. The MMP-2C solution structure is compared with MMP-8 crystal structure bound to the same inhibitor to highlight the differences especially in the S1' specificity loop. The finding provides a structural explanation for the selectivity between MMP-2 and MMP-8 that is achieved by large inhibitors.

PubMed: 12147339
DOI: 10.1016/S0167-4838(02)00307-2

Experimental method

SOLUTION NMR