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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Structure of Helicobacter pylori L-asparaginase at 1.4 ? resolution
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Structure of Helicobacter pylori L-asparaginase at 1.4 ? resolution

机译：幽门螺杆菌L-asparaginase结构1.4 ?

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摘要

Bacterial L-asparaginases have been used in the treatment of childhood acute lymphoblastic leukaemia for over 30 years. Their therapeutic effect is based on their ability to catalyze the conversion of L-asparagine, an essential amino acid in certain tumours, to L-aspartic acid and ammonia. Two L-aspara-ginases, one from Escherichia coli and the other from Erwinia chrysanthemi, have been widely employed in clinical practice as anti-leukaemia drugs. However, L-asparaginases are also able to cause severe side effects owing to their intrinsic glutaminase activity. Helicobacter pylori L-asparaginase (HpA) has been reported to have negligible glutaminase activity. To gain insight into the properties of HpA, its crystal structure in the presence of L-aspartate was determined to 1.4 ? resolution, which is one of the highest resolutions obtained for an L - asparaginase structure. The final structure has an Rcryst of 12.6% (Rfree = 16.9%) with good stereochemistry. A detailed analysis of the active site showed major differences in the active-site flexible loop and in the 286-297 loop from the second subunit, which is involved in active-site formation. Accordingly, Glu289, Asn255 and Gln63 are suggested to play roles in modulating the accessibility of the active site. Overall, the structural comparison revealed that HpA has greater structural similarity to E. coli L-asparaginase than to any other L-asparaginase, including Er. carotovora L-asparaginase, despite the fact that the latter is also characterized by low glutaminase activity.
机译：细菌L-asparaginases中使用治疗儿童急性淋巴细胞白血病了30多年。效果是基于他们的催化能力L-asparagine转换,一种必需氨基酸酸在某些肿瘤,天门冬氨酸氨。从欧文氏菌大肠杆菌和其他chrysanthemi,被广泛采用临床实践是anti-leukaemia药物。然而,L-asparaginases也能够引起由于其内在严重的副作用谷氨酰胺酶的活动。L-asparaginase (HpA)据报道微不足道的谷氨酰胺酶的活动。HpA的属性,它的晶体结构在L-aspartate决心的存在1.4 ?决议得到L -天冬酰胺酶结构。12.6% (Rfree = 16.9%)具有良好的立体化学。活性部位的详细分析主要区别在活性部位灵活循环,在286 - 297年从第二个循环亚基,这是参与活性部位形成。建议在调节中发挥作用可访问性的活性部位。结构的比较显示,HpA更大的结构相似性的大肠杆菌比其他L-asparaginase L-asparaginase,包括Er。后者也具有这一事实谷氨酰胺酶活性较低。

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