Functional analysis of the MbtH-like protein superfamily

MbtH 样蛋白超家族的功能分析

• 批准号: 8593304
• 负责人: Katrina T Forest
• 金额: $ 27.98万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-06 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8593304
• 关键词: Affect; Alanine; Amino Acids; Anabolism; Bacteria; Bacterial Physiology; Biochemistry; Biological Models; Code; Complex; Coupled; Data; Engineering; Enterobactin; Enzymatic Biochemistry; Enzymes; Escherichia coli; Eubacterium; Generations; Genetic Screening; Goals; Molecular; Multienzyme Complexes; Mycobacterium tuberculosis; Names; Nucleic Acid-Independent Peptide Biosynthesis; Pathway interactions; Peptide Synthesis; Peptides; Play; Production; Proteins; Role; Scanning; Serine; Site-Directed Mutagenesis; Solubility; Specificity; Structure; System; X-Ray Crystallography; abstracting; crosslink; drug development; genetic selection; in vivo; interest; member; metabolic engineering; mutant; mycobactins; next generation; peptide synthase; protein function; protein protein interaction; public health relevance; structural biology

DESCRIPTION (provided by applicant): PROJECT SUMMARY/ABSTRACT The MbtH-like protein (MLP) superfamily consists of relatively small proteins (60-80 amino acids) that are found only in eubacteria and are most commonly associated with nonribosomal peptide synthetases (NRPS). This superfamily is named after its founding member MbtH, which is a protein of unknown function in the mycobactin biosynthesis pathway in Mycobacterium tuberculosis. The common association of these proteins with NRPS systems suggested that they play some role in nonribosomal peptide production, but the prevailing view was that these proteins were not involved in the enzymology of NRPSs. Our recent data suggest this view needs to be revised since we have shown MLPs impact the solubility and function of heterologously overproduced NRPSs. Our overall goal is to understand how MPLs influence NRPS enzymology and how the MLP and NRPS interactions occur at the molecular level to provide general function and protein-protein interaction specificity. The results from this project will have a broad impact on the basic understanding of NRPS enzymology, the generation of new derivatives of nonribosomal peptides using metabolic engineering, the targeting of these enzymes for drug development, and the understanding of the role these proteins have on bacterial physiology.

描述（由申请人提供）：