The Computational and Experimental Study of Enzymes + LigandInteractions

异香豆素对弹性酶(人白细胞弹性酶(HLE)和猪胰腺弹性酶(PPE))有很强的抑制作用。结构和化学信息允许提出一种合理的行动机制。然而，优先结合模式是由特定的异香豆素衍生物与活性中心残基的一系列复杂的相互作用决定的。到目前为止，还没有两种同香豆素以相同的方式结合。为了更好地了解PPE与7-甲氧基-4-氯-3-甲氧基异香豆素的结合作用和选择性，我们将对其高分辨晶体结构进行研究。这是目前可用的最有效的弹性蛋白酶异香豆素抑制剂。结构将被改进，结构结果将被评估，并与其他弹性酶复合体的结构信息数据库相关。

Isocoumarins exhibit strong inhibition with elastases (human leucocyte elastase (HLE) and porcine pancreatic elastase (PPE)). Structural and chemical information permit a plausible mechanism to be proposed for action. The preferential binding mode, however, is dictated by a complex set of interactions of the specific isocoumarin derivative with the active site residues. To date, no two isocoumarins bind in the same way. In order better to understand binding interactions and preference the high-resolution crystal structure of 7-TosPhe-4-Cl-3-methoxy isocoumarin bound to PPE will be studied. This is the most potent isocoumarin inhibitor of elastase currently available. The structure will be refined and structural results will be evaluated and related to the database of structural information on other elastase complexes.