DIPHTHAMIDE BIOSYNTHESIS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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一种策略。双乙酰胺[2，3-羧氨基-3- (三甲基氨基)丙基组氨酸]是一种独特的修饰组氨酸残基，在真核生物和考古细菌的翻译延伸因子2中都发现保守。敌草胺的作用仍是研究的主题。例如，缺乏修饰的酵母突变株已被鉴定为具有不受抑制的生长和生存能力(Chen等人。摩尔。细胞生物。1985年)。然而，敌草胺残基似乎在蛋白质合成过程中具有防止-1移码的功能(Gomez-Lorenzo等人。也是白喉毒素和铜绿假单胞菌外毒素A的ADP核糖基化靶标。 敌草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和一种迄今尚未确定的酶，该酶执行最后的酰胺化步骤。第一步涉及S-腺苷甲硫氨酸的3-氨基-3-羧丙基的转移，涉及dph1-4酶。DPH-5催化氨基的三甲基化生成二苯乙胺，这是最后的酰胺化步骤的底物。 有趣的是，在考古细菌中只有2个基因产物被鉴定出参与双苯二甲胺的合成，DPH-2和DPH-5。为了深入了解敌草胺的生物合成途径，人们对古生菌DPH-2进行了结构研究。

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.