Protein patched homolog 1

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Revision as of 08:11, 6 February 2021

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spinqualitylabelsall models Human deoxypusine synthase with mercaptocysteine complex with spermidine, ethylene glycol, formate, acetate, mercaptoethanol, MPD (PDB code 6xxk) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Disease 3 Relevance 4 Structural highlights Function Protein patched homolog 1 (Ptch1) 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). Disease Mutations in DHS result in reduced enzyme activity that limit the hypusination of elf5A which is associated with neurodevelopmental disorder[2]. Relevance Inhibition of DHS may provide a strategy for reducing diabetogenic cells and preserving β cell function in type 1 diabetes[3]. Structural highlights The complex between DHS and its substrate spermidine shows the binding in the active site with spermidine forming hydrogen bonds to DHS with its 2 terminal amino groups [4].

3D Structures of protein patched homolog 1

Updated on 06-February-2021

6dmb, 6oeu – hPtch1 – human - Cryo EM
6dmo – hPtch1 (mutant) - Cryo EM
6rtx – hPtch1 ectodomain 1 139-428
6rty – hPtch1 ectodomain 1 + nanobody
6rvc – hPtch1 ectodomain 2 772-1023 + nanobody
6rtw – hPtch1 ectodomain 1 + nanobody + cholesterol derivative
6mg8 – Ptch1 + ligand – mouse - Cryo EM

References

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ Wator E, Wilk P, Grudnik P. Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase. Biomolecules. 2020 Mar 30;10(4). pii: biom10040522. doi: 10.3390/biom10040522. PMID:32235505 doi:http://dx.doi.org/10.3390/biom10040522