Structure and function of GlmU from Mycobacterium tuberculosis.
Structure and function of GlmU from Mycobacterium tuberculosis.
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DOI：
10.1107/s0907444909001036
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发表时间：
2009-03
期刊：
影响因子：
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通讯作者：
Zhening Zhang;E. M. Bulloch;R. D. Bunker;E. Baker;C. Squire
中科院分区：
文献类型：
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作者：
Zhening Zhang;E. M. Bulloch;R. D. Bunker;E. Baker;C. Squire
抗生素耐药性是结核病等传染病治疗中的一个主要问题。现有的抗生素仅针对少数细胞途径，迫切需要具有新分子机制的抗生素。glmU基因在结核分枝杆菌中是必不可少的，是最佳细菌生长所必需的，并且已被选择为用于结构和功能研究的可能的药物靶标。GlmU是催化从GlcN-I-P形成UDP-GlcNAc的双功能乙酰转移酶/尿苷酰转移酶。UDP-GlcNAc是两种重要生物合成途径的底物：脂多糖和肽聚糖合成。对M.结核病GlmU已被确定为未配体形式和与GlcNAc-1-P或UDP-GlcNAc复合。结构揭示了负责底物结合的残基。酶活性通过（1）H NMR表征，表明乙酰辅酶A的存在对尿苷酰转移酶活性具有抑制作用。
Antibiotic resistance is a major issue in the treatment of infectious diseases such as tuberculosis. Existing antibiotics target only a few cellular pathways and there is an urgent need for antibiotics that have novel molecular mechanisms. The glmU gene is essential in Mycobacterium tuberculosis, being required for optimal bacterial growth, and has been selected as a possible drug target for structural and functional investigation. GlmU is a bifunctional acetyltransferase/uridyltransferase that catalyses the formation of UDP-GlcNAc from GlcN-1-P. UDP-GlcNAc is a substrate for two important biosynthetic pathways: lipopolysaccharide and peptidoglycan synthesis. The crystal structure of M. tuberculosis GlmU has been determined in an unliganded form and in complex with GlcNAc-1-P or UDP-GlcNAc. The structures reveal the residues that are responsible for substrate binding. Enzyme activities were characterized by (1)H NMR and suggest that the presence of acetyl-coenzyme A has an inhibitory effect on uridyltransferase activity.