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The structural characterization of a glucosylglycerate hydrolase provides insights into the molecular mechanism of mycobacterial recovery from nitrogen starvation

机译:葡萄糖基甘油酸水解酶的结构表征提供了从氮饥饿中分枝杆菌回收的分子机制的见解

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Bacteria are challenged to adapt to environmental variations in order to survive. Under nutritional stress, several bacteria are able to slow down their metabolism into a nonreplicating state and wait for favourable conditions. It is almost universal that bacteria accumulate carbon stores to survive during this nonreplicating state and to fuel rapid proliferation when the growth-limiting stress disappears. Mycobacteria are exceedingly successful in their ability to become dormant under harsh circumstances and to be able to resume growth when conditions are favourable. Rapidly growing mycobacteria accumulate glucosylglycerate under nitrogen-limiting conditions and quickly mobilize it when nitrogen availability is restored. The depletion of intracellular glucosyl­glycerate levels in Mycolicibacterium hassiacum (basonym Mycobacterium hassiacum) was associated with the up-regulation of the gene coding for glucosylglycerate hydrolase (GgH), an enzyme that is able to hydrolyse glucosylglycerate to glycerate and glucose, a source of readily available energy. Highly conserved among unrelated phyla, GgH is likely to be involved in bacterial reactivation following nitrogen starvation, which in addition to other factors driving mycobacterial recovery may also provide an opportunity for therapeutic intervention, especially in the serious infections caused by some emerging opportunistic pathogens of this group, such as Mycobacteroides abscessus (basonym Mycobacterium abscessus). Using a combination of biochemical methods and hybrid structural approaches, the oligomeric organization of M. hassiacum GgH was determined and molecular determinants of its substrate binding and specificity were unveiled.
机译:细菌要适应环境变化才能生存。在营养压力下,几种细菌能够将其新陈代谢减慢至非复制状态,并等待有利的条件。在这种非复制状态下,细菌会积聚碳,以生存下来,并在生长限制压力消失时,促进快速扩散,这几乎是普遍现象。分枝杆菌在极端条件下休眠和在有利条件下恢复生长的能力非常成功。快速生长的分枝杆菌在氮限制的条件下积累了葡萄糖基甘油酸,当氮的可用性恢复时,其迅速动员。 hassiacum分枝杆菌中的细胞内葡萄糖基甘油水平的消耗与葡萄糖基甘油酸水解酶(GgH)编码基因的上调相关,该酶能够将葡萄糖基甘油酸水解为甘油和葡萄糖,这是一个容易获得的来源能源。 GgH在不相关的系中高度保守,很可能与氮饥饿后的细菌活化有关,除了驱动分枝杆菌恢复的其他因素外,GgH还可能提供治疗干预的机会,尤其是在某些新出现的机会性病原体引起的严重感染中组,例如脓肿分枝杆菌(Mycobacteroides abscessus)。使用生化方法和混合结构方法相结合,确定了镰刀菌GgH的低聚组织,并揭示了其底物结合和特异性的分子决定因素。

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