Mechanism and Inhibition of Matrix Metalloproteinases

被引:34
作者
Cerofolini, Linda [1 ,2 ]
Fragai, Marco [1 ,2 ,3 ]
Luchinat, Claudio [1 ,2 ,3 ]
机构
[1] Univ Florence, Magnet Resonance Ctr CERM, Via L Sacconi 6, I-50019 Sesto Fiorentino, Italy
[2] CIRMMP, Via L Sacconi 6, I-50019 Sesto Fiorentino, Italy
[3] Univ Florence, Dept Chem Ugo Schiff, Via Lastruccia 3-13,Via L Sacconi 6, I-50019 Sesto Fiorentino, Italy
基金
欧盟地平线“2020”;
关键词
Matrix metalloproteinases; enzyme; mechanism; collagenolysis; elastolysis; inhibitor; HUMAN NEUTROPHIL COLLAGENASE; HUMAN FIBROBLAST COLLAGENASE; C-TERMINAL DOMAIN; 1.8-ANGSTROM CRYSTAL-STRUCTURE; ACID-BASED INHIBITORS; ZINC-BINDING GROUPS; SOLID-STATE NMR; X-RAY-STRUCTURE; CATALYTIC-DOMAIN; EXTRACELLULAR-MATRIX;
D O I
10.2174/0929867325666180326163523
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Matrix metalloproteinases hydrolyze proteins and glycoproteins forming the extracellular ma- trix, cytokines and growth factors released in the extracellular space, and membrane-bound receptors on the outer cell membrane. The pathological relevance of MMPs has prompted the structural and functional characterization of these enzymes and the development of synthetic inhibitors as possible drug candidates. Recent studies have provided a better understanding of the substrate preference of the different members of the family, and structural data on the mechanism by which these enzymes hydrolyze the substrates. Here, we report the recent advancements in the understanding of the mechanism of collagenolysis and elastolysis, and we discuss the perspectives of new therapeutic strategies for targeting MMPs.
引用
收藏
页码:2609 / 2633
页数:25
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