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Crystal structure and function analysis of 6-phosphogluconate dehydrogenase in Mycobacterium tuberculosis

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机构: [1]Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, PR China [2]State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, PR China [3]Cancer Biotherapy Center & Cancer Research Institute, Peking University Cancer Hospital Yunnan, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650100, PR China
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关键词: Mycobacterium tuberculosis 6-Phosphogluconate dehydrogenase Crystal structure Enzymatic kinetics

摘要:
6-phosphogluconate dehydrogenase (6PGDH) is an essential enzyme in energy metabolism and redox reactions, and represents a potential drug target for the development of therapies targeting trypanosomes, plasmodium, or other pathogens. Tuberculosis, caused by Mycobacterium tuberculosis, is a contagious disease that severely affects human health, with approximately one-third of the world's population infected. However, the protein structure, exact oligomeric state, and catalytic mechanism of 6PGDH in Mycobacterium tuberculosis (Mt6PGDH) have remained largely unknown. In this study, we successfully purified and determined the structure of Mt6PGDH, revealing its function as a tetramer in both solution and crystal states. Through structural comparisons, we clarified the tetramer formation mechanism and the oligomeric organization of short-chain 6PGDHs. Additionally, we identified key residues for coenzyme recognition and catalytic activity. This work not only deepens our understanding of the enzymatic function of Mt6PGDH but also lays a foundation for the development of drugs targeting this enzyme.Copyright © 2024 Elsevier Inc. All rights reserved.

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出版当年[2023]版:
大类 | 3 区 生物学
小类 | 3 区 生物物理 4 区 生化与分子生物学
最新[2023]版:
大类 | 3 区 生物学
小类 | 3 区 生物物理 4 区 生化与分子生物学
第一作者:
第一作者机构: [1]Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, PR China [2]State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, PR China
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通讯机构: [1]Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, PR China [2]State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, PR China
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