Deoxyhypusine hydroxylase (DOHH) is a monomeric monooxygenase that catalyzes a critical reaction step of the unique protein modification called hypusination. Modified at a specific lysine residue, eukaryotic translation initiation factor 5a (eIF‐5A) is the only protein known to be hypusinated. The presence of the noncanonical amino acid hypusine in eIF‐5A is not only crucial for the activity of the protein and vital for eukaryotic cells, but is also involved in the pathogenesis of several diseases, such as cancer, AIDS, and diabetes. DOHH is therefore considered a novel target for the design of drugs against these major health threats. DOHH is a nonheme diiron enzyme that activates oxygen for substrate hydroxylation. Featuring a blue chromophore, the peroxo‐diiron(III) intermediate of human DOHH is unusually stable, allowing its crystallization and the first elucidation of a three‐dimensional structure of this intermediate in its native biological environment. The overall structure of DOHH comprises two pseudosymmetric domains, each consisting of four HEAT repeats. The structural information, in combination with spectroscopic analyses and comparison to other nonheme diiron enzymes, has been used to suggest a putative catalytic mechanism for DOHH. Compounds shown to inactivate DOHH include ciclopirox, mimosine, deferiprone, and zileuton.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.