de Oliveira Cesar Augusto F, Zissen Maurice, Mongon John, McCammon J Andrew
Howard Hughes Medical Institute, Center for Theoretical Biological Physics, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA.
Curr Pharm Des. 2007;13(34):3471-5. doi: 10.2174/138161207782794211.
Matrix Metalloproteinases (MMPs) are zinc-containing proteinases that are responsible for the metabolism of extracellular matrix proteins. Overexpression of MMPs has been associated with a wide range of pathological diseases such as arthritis, cancer, multiple sclerosis and Alzheimer's disease. The excessive and unregulated activity of Matrix Metalloproteinases type 2 (MMP-2), also known as gelatinase A, has been identified in a numbers of cancer metastases. Several MMP inhibitors (MMPi) have been proposed in the literature aiming to interfere in the MMPs activity. In this work we performed long MD simulations in order to study the dynamical behavior of the binding pocket S1' in the apo forms of MMP type 2 and 3, and identify, at the molecular level, the structural properties relevant for the designing of specific inhibitor of MMP-2.
基质金属蛋白酶（MMPs）是一类含锌蛋白酶，负责细胞外基质蛋白的代谢。MMPs的过表达与多种病理疾病相关，如关节炎、癌症、多发性硬化症和阿尔茨海默病。在许多癌症转移中已发现2型基质金属蛋白酶（MMP-2，也称为明胶酶A）的过度和不受调控的活性。文献中已提出几种MMP抑制剂（MMPi），旨在干扰MMPs的活性。在这项工作中，我们进行了长时间的分子动力学模拟，以研究2型和3型MMPs无配体形式中结合口袋S1'的动力学行为，并在分子水平上确定与设计MMP-2特异性抑制剂相关的结构特性。
