MATRIX METALLOPROTEINASE SOLUTION STRUCTURE BY NMR

通过 NMR 分析基质金属蛋白酶溶液结构

• 批准号: 2191410
• 负责人: ERIK R ZUIDERWEG
• 金额: $ 14.07万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2191410
• 关键词: active sites; biophysics; enzyme complex; enzyme structure; nuclear magnetic resonance spectroscopy; protease inhibitor; solutions; stromelysin; structural biology

DESCRIPTION: The matrix metallo proteinases (MMPs) are strongly implicated in abnormal tissue degradation. Specific pathologic roles of the MMPs type IV collagenase and stromelysin are to facilitate tumor metastasis and invasion by degradation of the cellular basement membranes.Stromelysin is also involved in the destruction of tissue associated with arthritic diseases. These factors generate a strong interest to understand the three-dimensional structure and function of the MMPs in detail and to develop specific inhibitors of these proteins. Recent developments in nuclear magnetic resonance (NMR) make solution structure determinations for proteins up to 25 kDa feasible. It is proposed to use these new techniques to determine the solution structure of the 20 kDa catalytic domain of stromelysin, complexed with an inhibitor. The interaction between a peptide representing the prosequence of the stromelysin and the catalytic domain will also be investigated by NMR. Extensive homologies of the stromelysin domain with similar regions in other members of MMP family suggest that the structure determination of this domain will help understand the functioning of the metallo proteinase family as a whole. The knowledge of the three-dimensional structure of the catalytic site of these enzymes should aid in the development of potential inhibitors against the MMPs.

描述：基质金属蛋白酶（MMP）强烈 与组织异常降解有关。 特定的病理作用 IV型胶原酶和Stromelysin的MMPS的促进 转移和通过降解细胞基底降解的侵袭 膜。斯特罗梅辛还参与了组织的破坏 与关节炎有关。这些因素产生了强大的 兴趣了解三维结构和功能 MMP详细并开发出特定的抑制剂 这些蛋白质。 核的最新发展 磁共振（NMR）进行溶液结构确定 对于可行的25 kDa的蛋白质。 建议使用这些新的 确定20 kDa催化的溶液结构的技术 Stromelysin的结构域，与抑制剂复合。 相互作用 在代表斯特罗米辛的序列的肽和肽之间 NMR还将研究催化结构域。 广泛的同源性 MMP其他成员中具有相似区域的Stromelysin域的 家庭建议该领域的结构确定将有助于 了解整个金属蛋白酶家族的功能。 催化位点的三维结构的知识 这些酶应有助于发展潜在抑制剂 针对MMP。