首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Structure of Staphylococcus aureus adenylosuccinate lyase (PurB) and assessment of its potential as a target for structure-based inhibitor discovery.
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Structure of Staphylococcus aureus adenylosuccinate lyase (PurB) and assessment of its potential as a target for structure-based inhibitor discovery.

机译:金黄色葡萄球菌的结构adenylosuccinate裂合酶(PurB)和评估其潜在的作为小的目标抑制剂的发现。

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摘要

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.
机译:的中分辨率结构从细菌adenylosuccinate裂合酶(PurB)病原体金黄色葡萄球菌在复杂AMP。结晶的产物,被模仿在活性位点和占据了一个位置琥珀酸是观察到同源结构。嘌呤和支持提供AMP /延胡索酸酯水平的控制。酶预测是必不可少的金黄色葡萄球菌和潜在的生存治疗的目标。PurB与大肠杆菌的酶提出了允许讨论有关酶的机制。建议密切相似的活性网站将很难识别这种酶的特异性抑制剂。然而,有不同的方式子单元组装成二聚体。可能会提供一个独特subunit-subunit接口目标通过利用的潜在区域观察到的酶活性网站依赖于寡聚化。

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