DIPHTHAMIDE BIOSYNTHESIS

敌草胺生物合成

• 批准号: 8169279
• 负责人: STEVEN E EALICK
• 金额: $ 0.24万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169279
• 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

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 翻译后的修饰可以多样化基因产物的功能特性，并且是生物学中普遍起来的策略。 Diphthamide [2,3-羧基二酰胺-3-- （三甲基氨基）丙氨氨酸]是一种独特的修饰组氨酸残基，在真核生物和古细菌的翻译伸长因子2中保守。 Diphthamide的功能仍然是研究的主题。 例如，缺乏修饰的酵母突变体已被鉴定出不受抑制的生长和生存能力（Chen等人CellBiol。1985）。 然而，双乙酰胺残基似乎在预防蛋白质合成过程中的-1架外（Gomez-Lorenzo等人Embo J. 2000）中具有功能，并且也是二骨毒素毒素的ADP-核糖基化靶标，以及pseudomonaseudomonasaassaisaaseosa exotoxin A. Diphthamide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和一种尚未确定的未鉴定酶，该酶执行了最终的脑集步骤。 第一步涉及从s-腺苷甲氨酸（SAM）转移3-氨基-3-羧基丙基，并涉及酶DPH1-4。 DPH-5催化氨基群的三甲基化形成二甲氨酸，这是最终抑制步骤的底物。 有趣的是，在考古细菌中仅鉴定了2种基因产物参与DIPHTHAMIDE合成，DPH-2和DPH-5。 为了深入了解双智酰胺生物合成途径，已经对考古学的DPH-2进行了结构研究。