1ks0
The First Fibronectin Type II Module from Human Matrix Metalloproteinase 2
|
OverviewOverview
Human matrix metalloproteinase-2 (MMP-2) contains three in-tandem, fibronectin type II (FII) repeats that bind gelatin. Here, we report the, NMR solution structure of the first FII module of MMP-2 (col-1). The, latter is described as a characteristic, globular FII fold containing two, beta-sheets, a stretch of 3(1)-helix, a turn of alpha-helix, and an, exposed hydrophobic surface lined with aromatic residues. We show that, col-1 binds (Pro-Pro-Gly)6, a mimic of gelatin, with a Ka of approx. 0.42, mm(-1), and that its binding site involves a number of aromatic residues, as well as Arg34, as previously found for the second and third homologous, repeats. Moreover, the affinity of the in-tandem col-1+2 construct, (col-12) toward the longer ligand (Pro-Pro-Gly)12 is twice that for, (Pro-Pro-Gly)6, as expected from mass action. A detailed structural, comparison between FII and kringle domains indicates that four main, conformational features are shared: two antiparallel beta-sheets, a, central 3(1)-helix, and the quasiperpendicular orientation of the two, proximal Cys-Cys bonds. Structure superposition by optimizing overlap of, cystine bridge areas results in close juxtaposition of their main, beta-sheets and 31-helices, and reveals that the gelatin binding site of, FII modules falls at similar locations and exhibits almost identical, topological features to those of the lysine binding site of kringle, domains. Thus, despite the minor (<15%) consensus sequence relating FII, modules to kringles, there is a strong folding and binding site structural, homology between the two domains, enforced by key common conformational, determinants.
DiseaseDisease
Known diseases associated with this structure: Osteolysis, idiopathic, Saudi type OMIM:[120360], Winchester syndrome OMIM:[120360]
About this StructureAbout this Structure
1KS0 is a Single protein structure of sequence from Homo sapiens. Active as Gelatinase A, with EC number 3.4.24.24 Full crystallographic information is available from OCA.
ReferenceReference
The col-1 module of human matrix metalloproteinase-2 (MMP-2): structural/functional relatedness between gelatin-binding fibronectin type II modules and lysine-binding kringle domains., Gehrmann M, Briknarova K, Banyai L, Patthy L, Llinas M, Biol Chem. 2002 Jan;383(1):137-48. PMID:11928808
Page seeded by OCA on Mon Nov 12 17:53:58 2007