HYPUSINE IN EIF-4D--BIOSYNTHESIS AND FUNCTION

真核蛋白翻译起始因子4D（eIF-4D）含有一个 这似乎是唯一的细胞蛋白质与此 一种独特的氨基酸 羟腐胺赖氨酸是由以下物质在产后产生的： 将多胺亚精胺的丁胺部分转移至赖氨酸 eIF-4D前体中的残基和随后的羟基化。 这些 研究结果揭示了一种新的细胞代谢途径。 比较 成熟eIF-4D的甲硫氨酰嘌呤霉素合成活性，eIF-4D 含有未修饰的赖氨酸代替羟腐胺赖氨酸的前体和 体外制备的含脱氧羟腐胺赖氨酸的eIF-4D衍生物 通过脱氧羟腐胺赖氨酸合酶修饰克隆的eIF-4D前体 表明脱氧羟腐胺赖氨酸或羟腐胺赖氨酸对于蛋白质 合成起始。 成熟的eIF-4D似乎对生长至关重要。 真核细胞 因此，羟腐胺赖氨酸生物合成步骤提供了一种生物合成方法。 用于干预细胞增殖特异性潜在靶点。 正在制备羟腐胺赖氨酸生物合成的特异性抑制剂。 研究 正在将羟腐胺的结构与生理联系起来 eIF-4D的功能及其在真核蛋白中的作用方式 合成.

Eukaryotic protein translation initiation factor 4D (eIF-4D) contains one residue of hypusine and appears to be the only cellular protein with this one unique amino acid. Hypusine is produced post-translationally by transfer of the butylamine portion of the polyamine spermidine to a lysine residue in the eIF-4D precursor and subsequent hydroxylation. These findings reveal a novel cellular metabolic pathway. Comparison of methionyl-puromycin sunthesis activities of mature eIF-4D, eIF-4D precursors that contain unmodified lysine in place of hypusine and a deoxyhypusine-containing derivative of eIF-4D prepared by in vitro modification of cloned eIF-4D precursor by deoxyhypusine synthase indicates that either deoxyhypusine or hypusine is essential for protein synthesis initiation. Mature eIF-4D appear to be vital for growth of eukaryotic cells. Thus, the hypusine biosynthetic step presents a specific potential target for intervention in cellular proliferation. Specific inhibitors of hypusine biosynthesis are being prepared. Studies are underway to relate the structure of hypusine to the physiological function of eIF-4D and to its mode of action in eukaryotic protein synthesis.