DIPHTHAMIDE BIOSYNTHESIS

敌草胺生物合成

• 批准号: 7955214
• 负责人: STEVEN E EALICK
• 金额: $ 0.25万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955214
• 关键词: ADP ribosylation; Anabolism; Archaea; Biology; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Diphtheria Toxin; Enzymes; Eukaryota; Funding; Grant; Growth; Histidine; Institution; Modification; Pathway interactions; Peptide Elongation Factor 2; Post-Translational Protein Processing; Process; Property; Protein Biosynthesis; Proteins; Pseudomonas aeruginosa toxA protein; Research; Research Personnel; Research Subjects; Resources; Source; Translations; United States National Institutes of Health; Yeasts; amidation; amino group; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。 邻苯二甲酰胺[2，3-羧酰胺基-3- [（三甲基铵基）丙基组氨酸]是在真核生物和古细菌的翻译延伸因子2中发现的保守的经化学修饰的组氨酸残基。 邻苯二胺的作用仍是研究的主题。 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，在蛋白质合成过程中，二苯二甲酰胺残基似乎具有防止-1移码的功能（Gomez-Lorenzo et al. 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。 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dph 1 -5和一种尚未鉴定的酶，该酶进行最后的酰胺化步骤。 第一步涉及从S-腺苷甲硫氨酸（SAM）转移3-氨基-3-羧丙基，并涉及酶dph 1 -4。 Dph-5催化氨基的三甲基化，形成最后酰胺化步骤的底物diphthine。 有趣的是，在古细菌中只发现了2种基因产物参与了联苯二酰胺的合成，dph-2和dph-5。 对古细菌dph-2进行了结构研究，以便深入了解联苯二酰胺的生物合成途径。