DIPHTHAMIDE BIOSYNTHESIS

敌草胺生物合成

• 批准号: 8361653
• 负责人: STEVEN E EALICK
• 金额: $ 0.23万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361653
• 关键词: ADP ribosylation; Anabolism; Archaea; Biology; Cells; Complex; Diphtheria Toxin; Enzymes; Eukaryota; Funding; Grant; Growth; Histidine; Modification; National Center for Research Resources; Pathway interactions; Peptide Elongation Factor 2; Post-Translational Protein Processing; Principal Investigator; Process; Property; Protein Biosynthesis; Proteins; Pseudomonas aeruginosa toxA protein; Research; Research Infrastructure; Research Subjects; Resources; S-Adenosylmethionine; Source; Translations; United States National Institutes of Health; Yeasts; amidation; amino group; cost; insight; mutant; prevent; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Post-translational modifications can diversify the functional properties of gene products and is a widely-utilized strategy in biology. Diphthamide [2,3-carboxyamido-3- (trimethylammonio)propyl histidine] is a uniquely-modified histidine residue found conserved in translation elongation factor 2 from both eukaryotes and archaebacteria. The function of diphthamide is still the subject of research. For example, yeast mutants lacking the modification have been identified with uninhibited growth and viability (Chen et al. Mol. Cell Biol. 1985). However, the diphthamide residue appears to have function in preventing -1 frameshifting during protein synthesis (Gomez-Lorenzo et al. EMBO J. 2000) and is also the ADP-ribosylation target of diphtheria toxin as well as Pseudomonas aeruginosa exotoxin A. The biosynthesis of diphthamide is a complex process that involves 6 proteins in eukaryotes, dph1-5 and an as-yet unidentified enzyme that performs a final amidation step. The first step involves the transfer of the 3-amino-3-carboxypropyl group from S-adenosylmethionine (SAM) and involves the enzymes dph1-4. Dph-5 catalyzes trimethylation of the amino group to form diphthine, the substrate for the final amidation step. Interestingly, only 2 gene products have been identified in archaebacteria to be involved in diphthamide synthesis, dph-2 and dph-5. Structural studies have been undertaken on archaebacterial dph-2 in order to provide insight into the diphthamide biosynthetic pathway.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 翻译后修饰可以使基因产物的功能特性多样化，是生物学中广泛使用的策略。 二邻苯二甲酰胺[2,3-羧酰胺-3- [(三甲基铵)丙基组氨酸]是一种独特修饰的组氨酸残基，在真核生物和古细菌的翻译延伸因子 2 中发现保守。 二苯胺的功能仍然是研究的课题。 例如，缺乏修饰的酵母突变体已被鉴定为具有不受抑制的生长和活力（Chen 等人 Mol. Cell Biol. 1985）。 然而，二苯甲酰胺残基似乎具有防止蛋白质合成过程中 -1 移码的功能（Gomez-Lorenzo 等人 EMBO J. 2000），并且也是白喉毒素以及铜绿假单胞菌外毒素 A 的 ADP-核糖基化靶标。 二邻苯二甲酰胺的生物合成是一个复杂的过程，涉及真核生物中的 6 种蛋白质、dph1-5 和执行最终酰胺化步骤的尚未鉴定的酶。 第一步涉及从 S-腺苷甲硫氨酸 (SAM) 转移 3-氨基-3-羧基丙基，并涉及酶 dph1-4。 Dph-5 催化氨基的三甲基化形成二菲，这是最终酰胺化步骤的底物。 有趣的是，在古细菌中仅鉴定出 2 个基因产物参与二苯胺合成，即 dph-2 和 dph-5。 对古细菌 dph-2 进行了结构研究，以深入了解二苯胺生物合成途径。