Fülöp V, Böcskei Z, Polgár L
Department of Biochemistry, Oxford Centre for Molecular Sciences, University of Oxford, United Kingdom.
Cell. 1998 Jul 24;94(2):161-70. doi: 10.1016/s0092-8674(00)81416-6.
Prolyl oligopeptidase is a large cytosolic enzyme that belongs to a new class of serine peptidases. The enzyme is involved in the maturation and degradation of peptide hormones and neuropeptides, which relate to the induction of amnesia. The 1.4 A resolution crystal structure is presented here. The enzyme contains a peptidase domain with an alpha/beta hydrolase fold, and its catalytic triad (Ser554, His680, Asp641) is covered by the central tunnel of an unusual beta propeller. This domain makes prolyl oligopeptidase an oligopeptidase by excluding large structured peptides from the active site. In this way, the propeller protects larger peptides and proteins from proteolysis in the cytosol. The structure is also obtained with a transition state inhibitor, which may facilitate drug design to treat memory disorders.
脯氨酰寡肽酶是一种大型胞质酶，属于一类新型丝氨酸肽酶。该酶参与肽激素和神经肽的成熟与降解，这与失忆的诱导有关。本文展示了分辨率为1.4埃的晶体结构。该酶包含一个具有α/β水解酶折叠的肽酶结构域，其催化三联体（Ser554、His680、Asp641）被一个不寻常的β螺旋桨的中央通道所覆盖。这个结构域通过将大的结构化肽排除在活性位点之外，使脯氨酰寡肽酶成为一种寡肽酶。通过这种方式，螺旋桨可保护较大的肽和蛋白质在胞质溶胶中不被蛋白水解。该结构也是通过一种过渡态抑制剂获得的，这可能有助于设计治疗记忆障碍的药物。
