Intra- and Interdomain Flexibility in Matrix Metalloproteinases: Functional Aspects and Drug Design

被引：21

作者：

Bertini, Ivano ^{[1
,2
]}

Fragai, Marco ^{[1
,3
]}

Luchinat, Claudio ^{[1
,3
]}

机构：

[1] Univ Florence, Magnet Resonance Ctr CERM, I-50019 Sesto Fiorentino, Italy

[2] Univ Florence, Dept Chem, I-50019 Sesto Fiorentino, Italy

[3] Univ Florence, Dept Agr Biotechnol, I-50144 Florence, Italy

来源：

CURRENT PHARMACEUTICAL DESIGN | 2009年 / 15卷 / 31期

关键词：

Matrix metalloproteinases; NMR; SAXS; protein dynamics; protein flexibility; protease inhibitors; structure based drug design; HUMAN NEUTROPHIL COLLAGENASE; ZINC-BINDING GROUPS; X-RAY STRUCTURES; EXTRACELLULAR-MATRIX; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; SELECTIVE-INHIBITION; STRUCTURAL BASIS; IV COLLAGENASE; SUBSTRATE-SPECIFICITY;

D O I：

10.2174/138161209789271852

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Matrix metalloproteinases are involved in many biological processes and in a large set of diseases. In the last twenty years the genetics, functions, and the structural features of this family of proteolytic enzymes have been investigated and a large number of synthetic inhibitors designed and tested. A better knowledge of the dynamical features of these proteins can be relevant not only to reveal new biological activities but also to design more specific and selective inhibitors. Here, we report the common and the distinct structural features of these proteins, the most recent published information on protein dynamics in matrix metalloproteinases and the recent results on the catalytic mechanism. The implications of the observed intra- and interdomain flexibility in matrix metalloproteinases for drug design have been analyzed and discussed.

引用

页码：3592 / 3605

页数：14

共 135 条

[1]

Zinc-binding groups modulate selective inhibition of MMPs [J].