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
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
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DOI：
10.1515/bc.2002.014
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发表时间：
2002-01-01
影响因子：
3.7
通讯作者：
Llinás, M
中科院分区：
文献类型：
--
作者：
Gehrmann, M;Briknarová, K;Llinás, M
人基质金属蛋白酶-2（MMP-2）含有三个串联的与明胶结合的IF型纤连蛋白（FIB）重复序列。在这里，我们报告了MMP-2的第一个填充模块（col-1）的NMR溶液结构。后者被描述为特征性的球状填充折叠，包含两个β-折叠、一段3（1）-螺旋、一圈α-螺旋和衬有芳香残基的暴露的疏水表面。我们表明，col-1结合（Pro-Pro-Gly）（6），明胶的模拟物，K-a约为。0.42 mM（-1），并且其结合位点涉及许多芳香族残基以及Arg（34），如先前在第二和第三同源重复中发现的。此外，串联col-12构建体（col-12）对较长配体（Pro-Pro-Gly）（12）的亲和力是对（Pro-Pro-Gly）6的亲和力的两倍，如质量作用所预期。填充和kringle结构域之间的详细结构比较表明，四个主要的构象特征是共享的：两个反平行的β-折叠，一个中心3（1）-螺旋，和两个近端Cys-Cys键的准垂直取向。通过优化胱氨酸桥区域重叠的结构叠加导致其主要β-折叠和3（1）-螺旋的紧密并列，并揭示填充模块福尔斯的明胶结合位点落在类似的位置，并表现出与Kringle结构域的赖氨酸结合位点几乎相同的拓扑特征。虽然，小（
Human matrix metalloproteinase-2 (MMP-2) contains three in-tandem fibronectin type If (FII) repeats that bind gelatin. Here, we report the NMR solution structure of the first Fill module of MMP-2 (col-1). The latter is described as a characteristic, globular Fill 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 K-a of approx. 0.42 mM(-1), and that its binding site involves a number of aromatic residues as well as Arg(34), as previously found for the second and third homologous repeats. Moreover, the affinity of the in-tandem col-12 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 Fill 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 3(1)-helices, and reveals that the gelatin binding site of Fill 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 (