Evaluating mycothiolation of xenobiotics

评估外源性物质的霉菌硫醇化

• 批准号: 10132237
• 负责人: Donald R Ronning
• 金额: $ 18.64万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10132237
• 关键词: Actinobacteria class; Amides; Anabolism; Antibiotic Resistance; Antibiotics; Bacteria; Binding; Biochemical; Catalysis; Complex; Cysteine; Defense Mechanisms; Disease; Distal; Drug Metabolic Detoxication; Drug resistance; Drug usage; Enzymes; Ethionamide; Exhibits; Future; Genus Mycobacterium; Glucosamine; Goals; Homeostasis; In Vitro; Knock-out; Maps; Metal Binding Site; Molecular Weight; Mycobacterium Infections; Mycobacterium tuberculosis; Oxidation-Reduction; Pathway interactions; Pharmaceutical Preparations; Play; Predisposition; Process; Prodrugs; Reaction; Rifampin; Roentgen Rays; Role; Streptomycin; Structure; Sulfhydryl Compounds; Surface; System; Therapeutic; Transferase; Tuberculosis; Vancomycin; Xenobiotics; amidase; drug metabolism; drug modification; insight; interest; isoniazid; liquid chromatography mass spectrometry; mycobacterial; nitrocefin; pathogen; recruit; resistant strain; tuberculosis drugs

Mycothiol (MSH) is a small molecular weight biomolecule used to modify drugs in the Actinobacteria phylum. Mycobacterium tuberculosis (Mtb) produces the greatest intracellular concentrations of this unique thiol-containing biomolecule. Interest regarding MSH biosynthesis in Mtb is due to its importance in redox homeostasis in the bacterium as well as the role of mycothiol in neutralizing antibiotics used to treat Mtb infections. The mycothiol S-transferase (MST) enzyme that catalyzes the conjugation of MSH to a variety of compounds has been identified. Considering the prominent role of mycothiol in Mtb drug metabolism, a deeper understanding of the structure and function of MST will lead to a clearer understanding of this important defense mechanism that promotes antibiotic resistance in Mtb.

真菌硫醇（Mycothiol，MSH）是放线菌中一种用于修饰药物的小分子生物分子 门结核分枝杆菌（Mtb）产生最大的细胞内浓度， 独特的含巯基生物分子。对Mtb中MSH生物合成的兴趣是由于其 细菌中氧化还原稳态的重要性以及真菌硫醇在中和中的作用 用于治疗结核杆菌感染的抗生素。真菌硫醇S-转移酶（MST）催化 已经鉴定了MSH与多种化合物的缀合。考虑到联合国的突出作用， mycothiol在结核分枝杆菌药物代谢中的作用，深入了解mST的结构和功能， 从而更清楚地了解这种促进抗生素产生重要防御机制 抗结核菌