Crystal structure of the peroxo-diiron(III) intermediate of Deoxyhypusine hydroxylase, an oxygenase involved in hypusination

ZHENGGANG HAN; NAOKI SAKAI; LARS BOETTGER; SEBASTIÁN KLINKE; JOACHIM HAUBER; ALFRED TRAUTWEIN; ROLF HILGENFELD

STRUCTURE WITH FOLDING & DESIGN.

CELL PRESS

Lugar: United States; Año: 2015 vol. 23 p. 882 - 892

0969-2126

Deoxyhypusine hydroxylase (DOHH) is a non-heme diiron enzyme involved in the posttranslational modification of a critical lysine residue of eukaryotic translation initiation factor 5A (eIF-5A) to yield the unusual amino acid residue hypusine. This modification is essential for the role of eIF-5A in translation and in nuclear export of a group of specific mRNAs. The diiron center of human DOHH (hDOHH) forms a peroxo-diiron(III) intermediate (hDOHH-peroxo) when its reduced form reacts with O2. hDOHH-peroxo has a lifetime exceeding that of the peroxo intermediates of other diiron enzymes by several orders of magnitude. Here we report the 1.7-A crystal structures of hDOHH-peroxo and a complex with glycerol. The structure of hDOHH-peroxo reveals the presence of a mu-1,2-peroxo-diiron(III) species at the active site. Augmented by UV/Vis and Mossbauer spectroscopic studies, the crystal structures offer explanations for the extreme longevity of hDOHHperoxo and illustrate how the enzyme specifically recognizes its only substrate, deoxyhypusine-eIF-5A.