Spermidine lysine

Hypusine (Ne-(4-amino-2-hydroxybutyl)lysine)242 occurs in mammalian initiation factor 4D, which is utilized in protein synthesis (Chapter 29) and is formed by transfer of the 4-carbon butylamine group from spermidine to a lysine side chain followed by hydroxylation 280 2823 The lupine alkaloid lupinine283 is formed from two C5 units of cadaverine which arises by decarboxylation of lysine. Silaffins (pp. 178, 1381) also contain modified lysines. 

It is interesting to note that tallysomydn A has an additional amino acid, L-0-lysine, between the VI part and spermidine. 

Once correct positioning occurs, and the match is made between the anticodon of the met-tRNA and the start codon, the GTP molecule bound to eIF-2 is hydrolyzed in a reaction promoted by eIF-5. The physical nature of this reaction remains controversial. There are thought to be two forms of eIF-5 with molecular masses of 125 kDa and 60 kDa without, however, any differences in their biological properties (Hershey, 1991 Merrick, 1992). The hydrolysis of GTP causes the release of the initiation factors from the surface of the 40S ribosomal subunit, and allows attachment of the 60S subunit by triggering the release of eIF-6 from it. The formation of the SOS initiation complex culminates in the formation of the first peptide bond at the ribosomal P site. The initiation factor eIF-4D is required for the formation of the first peptide bond. eIF-4D is a small protein (about 16 kDa), and has a unique posttranslational modification of its lysine-50 residue by the action of a polyamine, spermidine, to form a hypusine residue essential for its activity (Hershey, 1991 Merrick, 1992). Furthermore, in order to allow efficient and catalytic use of eIF-2 after GTP hydrolysis and its release from the complex, another factor, eIF-2B, facilitates the exchange of eIF-2 bound GDP for GTP. 

The relationship between deoxyhypusine synthase and homospermidine synthase becomes also evident by a comparison of their reactions. Deoxyhypusine synthase transfers the aminobutyl moiety of spermidine to the e-amino group of a single specific lysine residue in the elF-5A (Fig. 18). Homospermidine synthase catalyzes exactly the same reaction but uses putrescine instead of the elF-5A as acceptor for the aminobutyl moiety (Fig. 18). AH other mechanistic... 

HSS exhibits strong sequence similarity to deoxyhypusine synthase (DHS), a ubiquitous enzyme responsible for the activation of eukaryotic initiation factor 5A (elFSA) (Ober and Hartmann 1999). DHS catalyses the transfer of an aminobutyl moiety from spermidine to a lysine residue of elFSA. In contrast, HSS does not accept elFSA as a substrate. However, HSS and DHS both catalyse the formation of homospermidine by the aminobutylation of putrescine, although this reaction is rarely catalysed by DHS in vivo. HSS is thought to have evolved from DHS after duplication of the single-copy dhs gene. The product lost the ability to bind and react with elFSA but retained HSS activity. HSS is a well-documented example of the evolutionary recruitment of a primary metabolic enzyme into a secondary metabolic pathway. 

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