Fyfe Paul K, Dawson Alice, Hutchison Marie Theres, Cameron Scott, Hunter William N
Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD15EH, Scotland.
Acta Crystallogr D Biol Crystallogr. 2010 Aug;66(Pt 8):881-8. doi: 10.1107/S0907444910020081. Epub 2010 Jul 9.
The medium-resolution structure of adenylosuccinate lyase (PurB) from the bacterial pathogen Staphylococcus aureus in complex with AMP is presented. Oxalate, which is likely to be an artifact of crystallization, has been modelled in the active site and occupies a position close to that where succinate is observed in orthologous structures. PurB catalyzes reactions that support the provision of purines and the control of AMP/fumarate levels. As such, the enzyme is predicted to be essential for the survival of S. aureus and to be a potential therapeutic target. Comparisons of this pathogen PurB with the enzyme from Escherichia coli are presented to allow discussion concerning the enzyme mechanism. Comparisons with human PurB suggest that the close similarity of the active sites would make it difficult to identify species-specific inhibitors for this enzyme. However, there are differences in the way that the subunits are assembled into dimers. The distinct subunit-subunit interfaces may provide a potential area to target by exploiting the observation that creation of the enzyme active site is dependent on oligomerization.
展示了来自细菌病原体金黄色葡萄球菌的腺苷酸琥珀酸裂解酶（PurB）与AMP复合物的中等分辨率结构。草酸盐可能是结晶的假象，已在活性位点进行建模，其占据的位置与在直系同源结构中观察到琥珀酸的位置相近。PurB催化支持嘌呤供应和控制AMP/富马酸水平的反应。因此，预计该酶对金黄色葡萄球菌的存活至关重要，并且是一个潜在的治疗靶点。本文对该病原体的PurB与大肠杆菌的酶进行了比较，以便讨论酶的作用机制。与人类PurB的比较表明，活性位点的高度相似性使得难以鉴定该酶的物种特异性抑制剂。然而，亚基组装成二聚体的方式存在差异。不同的亚基-亚基界面可能提供一个潜在的靶向区域，这是基于酶活性位点的形成依赖于寡聚化这一观察结果。
