An integrated structural and biophysical approach to study carbon metabolism in Mycobacterium tuberculosis.

Q3 Biochemistry, Genetics and Molecular Biology
QRB Discovery Pub Date : 2025-03-12 eCollection Date: 2025-01-01 DOI:10.1017/qrd.2025.6
Evelyn Y-W Huang, Francis Kuang, Haozhe Wu, Chai Xin Yu, Xiaoxu Chen, Glenda Vasku, Le Thao Anh Nguyen, Katherine J Jeppe, Anna K Coussens, Brooke X C Kwai, Ivanhoe K H Leung
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引用次数: 0

Abstract

Metabolic enzymes are the catalysts that drive the biochemical reactions essential for sustaining life. Many of these enzymes are tightly regulated by feedback mechanisms. To fully understand their roles and modulation, it is crucial to investigate the relationship between their structure, catalytic mechanism, and function. In this perspective, by using three examples from our studies on Mycobacterium tuberculosis (Mtb) isocitrate lyase and related proteins, we highlight how an integrated approach combining structural, activity, and biophysical data provides insights into their biological functions. These examples underscore the importance of employing fast-fail experiments at the early stages of a research project, emphasise the value of complementary techniques in validating findings, and demonstrate how in vitro data combined with chemical, biochemical, and physiological knowledge can lead to a broader understanding of metabolic adaptations in pathogenic bacteria. Finally, we address the unexplored questions in Mtb metabolism and discuss how we expand our approach to include microbiological and bioanalytical techniques to further our understanding. Such an integrated and interdisciplinary strategy has the potential to uncover novel regulatory mechanisms and identify new therapeutic opportunities for the eradication of tuberculosis. The approach can also be broadly applied to investigate other biochemical networks and complex biological systems.

综合结构和生物物理方法研究结核分枝杆菌的碳代谢。
代谢酶是驱动维持生命所必需的生化反应的催化剂。这些酶中的许多都受到反馈机制的严格调控。为了充分了解它们的作用和调控,研究它们的结构、催化机理和功能之间的关系至关重要。从这个角度来看,通过使用我们研究结核分枝杆菌(Mtb)异柠檬酸裂解酶和相关蛋白的三个例子,我们强调了如何将结构,活性和生物物理数据结合起来的综合方法提供了对其生物学功能的见解。这些例子强调了在研究项目的早期阶段采用快速失败实验的重要性,强调了互补技术在验证发现中的价值,并展示了如何将体外数据与化学、生化和生理学知识相结合,从而更广泛地了解致病菌的代谢适应。最后,我们解决了结核分枝杆菌代谢中未探索的问题,并讨论了如何扩展我们的方法,包括微生物学和生物分析技术,以进一步我们的理解。这种综合的跨学科战略有可能发现新的调节机制,并为根除结核病确定新的治疗机会。该方法也可以广泛应用于研究其他生化网络和复杂的生物系统。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
QRB Discovery
QRB Discovery Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
3.60
自引率
0.00%
发文量
18
审稿时长
12 weeks
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