| Structural highlights
Function
DOHH_HUMAN Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-L-lysine intermediate to form hypusine, an essential post-translational modification only found in mature eIF-5A factor.[HAMAP-Rule:MF_03101][1] [2]
Publication Abstract from PubMed
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 (hDOHHperoxo) when its reduced form reacts with O2. hDOHHperoxo 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 hDOHHperoxo and a complex with glycerol. The structure of hDOHHperoxo 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.
Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination.,Han Z, Sakai N, Bottger LH, Klinke S, Hauber J, Trautwein AX, Hilgenfeld R Structure. 2015 Apr 9. pii: S0969-2126(15)00080-5. doi:, 10.1016/j.str.2015.03.002. PMID:25865244[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Park JH, Aravind L, Wolff EC, Kaevel J, Kim YS, Park MH. Molecular cloning, expression, and structural prediction of deoxyhypusine hydroxylase: a HEAT-repeat-containing metalloenzyme. Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):51-6. Epub 2005 Dec 21. PMID:16371467 doi:http://dx.doi.org/0509348102
- ↑ Vu VV, Emerson JP, Martinho M, Kim YS, Munck E, Park MH, Que L Jr. Human deoxyhypusine hydroxylase, an enzyme involved in regulating cell growth, activates O2 with a nonheme diiron center. Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14814-9. doi:, 10.1073/pnas.0904553106. Epub 2009 Aug 19. PMID:19706422 doi:http://dx.doi.org/10.1073/pnas.0904553106
- ↑ Han Z, Sakai N, Bottger LH, Klinke S, Hauber J, Trautwein AX, Hilgenfeld R. Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination. Structure. 2015 Apr 9. pii: S0969-2126(15)00080-5. doi:, 10.1016/j.str.2015.03.002. PMID:25865244 doi:http://dx.doi.org/10.1016/j.str.2015.03.002
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