STROMELYSIN-1 - 3-DIMENSIONAL STRUCTURE OF THE INHIBITED CATALYTIC DOMAIN AND OF THE C-TRUNCATED PROENZYME
STROMELYSIN-1 - 3-DIMENSIONAL STRUCTURE OF THE INHIBITED CATALYTIC DOMAIN AND OF THE C-TRUNCATED PROENZYME
复制标题
DOI：
10.1002/pro.5560041002
复制
发表时间：
1995-10-01
期刊：
影响因子：
8
通讯作者：
SPRINGER, JP
中科院分区：
文献类型：
--
作者：
BECKER, JW;MARCY, AI;SPRINGER, JP
蛋白水解酶基质金属蛋白酶- 1是基质金属蛋白酶家族的一员，被认为在关节炎和肿瘤侵袭等病理条件中发挥作用。Stromelysin-1是一种通过去除n端原域而激活的原酶。该活性酶含有催化结构域和c端血红素结构域，被认为参与大分子底物识别。通过x射线衍射分析，我们确定了c -截断形式的原酶和催化结构域的抑制复合物的三维结构。催化核在两种形式中非常相似，与成纤维细胞和中性粒细胞胶原酶的同源结构域相似，也与核磁共振测定的基质溶酶结构相似。原结构域是一个独立的折叠单元，包含三个α -螺旋和位于酶活性部位的延伸肽。令人惊讶的是，该肽链的氨基-羧基方向与抑制剂和先前报道的胶原酶抑制剂所采用的方向相反。对比基质溶素和热溶素的活性位点发现，在热溶素酶促机制中发挥重要作用的残基，大多数在基质溶素中都有相应的残基，但与热溶素催化机制有关的三个残基在基质溶素中没有体现出来。
The proteolytic enzyme stromelysin-l is a member of the family of matrix metalloproteinases and is believed to play a role in pathological conditions such as arthritis and tumor invasion. Stromelysin-1 is synthesized as a proenzyme that is activated by removal of an N-terminal prodomain. The active enzyme contains a catalytic domain and a C-terminal hemopexin domain believed to participate in macromolecular substrate recognition. We have determined the three-dimensional structures of both a C-truncated form of the proenzyme and an inhibited complex of the catalytic domain by X-ray diffraction analysis. The catalytic core is very similar in the two forms and is similar to the homologous domain in fibroblast and neutrophil collagenases, as well as to the stromelysin structure determined by NMR. The prodomain is a separate folding unit containing three alpha-helices and an extended peptide that lies in the active site of the enzyme. Surprisingly, the amino-to-carboxyl direction of this peptide chain is opposite to that adopted by the inhibitor and by previously reported inhibitors of collagenase. Comparison of the active site of stromelysin with that of thermolysin reveals that most of the residues proposed to pray significant roles in the enzymatic mechanism of thermolysin have equivalents in stromelysin, but that three residues implicated in the catalytic mechanism of thermolysin are not represented in stromelysin.