2j0t
CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF MMP-1 IN COMPLEX WITH THE INHIBITORY DOMAIN OF TIMP-1
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OverviewOverview
The mammalian collagenases are a subgroup of the matrix metalloproteinases, (MMPs) that are uniquely able to cleave triple helical fibrillar, collagens. Collagen breakdown is an essential part of extracellular matrix, turnover in key physiological processes including morphogenesis and wound, healing; however, unregulated collagenolysis is linked to important, diseases such as arthritis and cancer. The tissue inhibitors of, metalloproteinases (TIMPs) function in controlling the activity of MMPs, including collagenases. We report here the structure of a complex of the, catalytic domain of fibroblast collagenase (MMP-1) with the N-terminal, inhibitory domain of human TIMP-1 (N-TIMP-1) at 2.54 A resolution., Comparison with the previously reported structure of the, TIMP-1/stromelysin-1 (MMP-3) complex shows that the mechanisms of, inhibition of both MMPs are generally similar, yet there are significant, differences in the protein-protein interfaces in the two complexes., Specifically, the loop between beta-strands A and B of TIMP-1 makes, contact with MMP-3 but not with MMP-1, and there are marked differences in, the roles of individual residues in the C-D connector of TIMP-1 in binding, to the two MMPs. Structural rearrangements in the bound MMPs are also, strikingly different. This is the first crystallographic structure that, contains the truncated N-terminal domain of a TIMP, which shows only minor, differences from the corresponding region of the full-length protein., Differences in the interactions in the two TIMP-1 complexes provide a, structural explanation for the results of previous mutational studies and, a basis for designing new N-TIMP-1 variants with restricted specificity.
DiseaseDisease
Known diseases associated with this structure: COPD, rate of decline of lung function in OMIM:[120353], Sorsby fundus dystrophy OMIM:[188826]
About this StructureAbout this Structure
2J0T is a Protein complex structure of sequences from Homo sapiens with ZN and CA as ligands. Active as Interstitial collagenase, with EC number 3.4.24.7 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the catalytic domain of matrix metalloproteinase-1 in complex with the inhibitory domain of tissue inhibitor of metalloproteinase-1., Iyer S, Wei S, Brew K, Acharya KR, J Biol Chem. 2007 Jan 5;282(1):364-71. Epub 2006 Oct 18. PMID:17050530
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