Deoxyhypusine synthase: Difference between revisions
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== Function == | == Function == | ||
'''Deoxyhypusine synthase''' (DHS) | '''Deoxyhypusine synthase''' (DHS) catalyzes the biosynthesis of deoxyhypusine by transfer of 4-aminobutyl moiety of spermidine to a specific Lys residue of initiation factor 4D<ref>PMID:2108161</ref>. Hypusine is formed post-translationally and is found in translation initiation factor 5A (elf5A). | ||
== Disease == | == Disease == | ||
Mutations in DHS result in reduced enzyme activity that limits the hypusination of elf5A which is associated with neurodevelopmental disorder<ref>PMID:30661771</ref>. | |||
==Relevance == | |||
Inhibition of DHS may provide a strategy for reducing diabetogenic cells and preserving β cell function in type 1 diabetes<ref>PMID:24196968</ref>. | |||
== Structural highlights == | == Structural highlights == | ||
Revision as of 14:16, 4 February 2021
FunctionDeoxyhypusine synthase (DHS) catalyzes the biosynthesis of deoxyhypusine by transfer of 4-aminobutyl moiety of spermidine to a specific Lys residue of initiation factor 4D[1]. Hypusine is formed post-translationally and is found in translation initiation factor 5A (elf5A). DiseaseMutations in DHS result in reduced enzyme activity that limits the hypusination of elf5A which is associated with neurodevelopmental disorder[2]. RelevanceInhibition of DHS may provide a strategy for reducing diabetogenic cells and preserving β cell function in type 1 diabetes[3]. Structural highlightsThe hydrophobic groove of the FERM domain of Rdx binds the N-terminal peptide of the adhesion molecule P-selectin glycoprotein ligand 1 with multiple hydrogen bonds[4]. Hydrophobic, Polar |
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3D Structures of deoxyhypusine synthase3D Structures of deoxyhypusine synthase
Updated on 04-February-2021
6xxh – hDHS – human
1dhs, 1rlz, 1roz, 6dft, 6xxi – hDHS + NAD
6xxm – hDHS + putrescine
6pgr, 6wkz, 6wl6 – hDHS + inhibitor
6xxl – hDHS + spermine
6xxk – hDHS + spermidine
6xxj – hDHS + NAD + spermidine
1rqd, 6prv – hDHS + NAD + inhibitor
7cmc – DHS + NAD - Pyrococcus horikishii
6w3z – DHS + NAD – Brugia malayi
ReferencesReferences
- ↑ Wolff EC, Park MH, Folk JE. Cleavage of spermidine as the first step in deoxyhypusine synthesis. The role of NAD. J Biol Chem. 1990 Mar 25;265(9):4793-9. PMID:2108161
- ↑ Ganapathi M, Padgett LR, Yamada K, Devinsky O, Willaert R, Person R, Au PB, Tagoe J, McDonald M, Karlowicz D, Wolf B, Lee J, Shen Y, Okur V, Deng L, LeDuc CA, Wang J, Hanner A, Mirmira RG, Park MH, Mastracci TL, Chung WK. Recessive Rare Variants in Deoxyhypusine Synthase, an Enzyme Involved in the Synthesis of Hypusine, Are Associated with a Neurodevelopmental Disorder. Am J Hum Genet. 2019 Feb 7;104(2):287-298. doi: 10.1016/j.ajhg.2018.12.017. Epub , 2019 Jan 17. PMID:30661771 doi:http://dx.doi.org/10.1016/j.ajhg.2018.12.017
- ↑ Colvin SC, Maier B, Morris DL, Tersey SA, Mirmira RG. Deoxyhypusine synthase promotes differentiation and proliferation of T helper type 1 (Th1) cells in autoimmune diabetes. J Biol Chem. 2013 Dec 20;288(51):36226-35. doi: 10.1074/jbc.M113.473942. Epub, 2013 Nov 6. PMID:24196968 doi:http://dx.doi.org/10.1074/jbc.M113.473942
- ↑ . PMID:18706570