Deoxyhypusine hydroxylase

Keywords Deoxyhypusine hydroxylase (DOHH) (DHS) elFSA Hypusine Spermidine Translation... 

The biosynthesis of hypusine (Scheme 10.1) is catalyzed by two specific enzymes, deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) (Park 2006 Wolff et al. 2007). DHS catalyzes an NAD-dependent cleavage of spermidine with the transfer of its 4-aminobutyl moiety to the terminal N of a specific lysine of elF5A (Lys 50 in human, Lys 51 in yeast) to form an intermediate, deoxyhypusine residue. Importantly, neither putrescine nor spermine can substitute for spermidine as a substrate, emphasizing the critical role of spermidine in cell growth. 

Kemper WM, Berry KW, Merrick WC (1976) Purification and properties of rabbit reticulocyte protein synthesis initiation factors M2Balpha and M2Bbeta. J Biol Chem 251 5551-5557 Kim SC, Sprung R, Chen Y et al (2006a) Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23 607-618 Kim YS, Kang KR, Wolff EC d al (2006b) Deoxyhypusine hydroxylase is a Fe(ll)-dependent, HEAT-repeat enzyme. Identification of amino acid residues critical for Fe(II) binding and catalysis [corrected]. J Biol Chem 281 13217—13225... 

Park JH, Aravind L, Wolff EC et al (2006) Molecular cloning, expression, and structural prediction of deoxyhypusine hydroxylase a HEAT-repeat-containing metalloenzyme. Proc Natl Acad Sci USA 103 51-56... 

Patel PH, Costa-Mattioli M, Schulze KL et al (2009) The Drosophila deoxyhypusine hydroxylase homologue nero and its target eIF5A are required for cell growth and the regulation of autoph-agy. J Cell Biol 185 1181-1194... 

The second enzyme, DOHH, irreversibly adds a hydroxyl group to the side chain of deoxyhypusine (Park et al. 2006 Park 2006). Like DHS, it is entirely specific for its protein substrate. It is an Fe(II)-dependent monooxygenase with a superhelical structure and a reaction mechanism distinct from other known protein hydroxylases (Kim et al. 2006b). 

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