peptidyl-lysine modification to peptidyl-hypusine
Definition
Target type: biologicalprocess
The modification of peptidyl-lysine to form hypusine, peptidyl-N6-(4-amino-2-hydroxybutyl)-L-lysine. [GOC:ma, ISBN:0198547684, RESID:AA0116]
The conversion of peptidyl-lysine to peptidyl-hypusine is a unique post-translational modification that occurs in a specific lysine residue within the eukaryotic initiation factor 5A (eIF5A). This modification is essential for the translation of a subset of mRNAs, particularly those encoding proteins required for cell growth and proliferation.
The process involves two key enzymes: deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH).
1. **DHS-catalyzed reaction:** DHS initiates the process by transferring the 4-aminobutyl moiety from the precursor molecule spermidine to the ε-amino group of a specific lysine residue within eIF5A, forming deoxyhypusine.
2. **DOHH-catalyzed reaction:** DOHH then oxidizes the deoxyhypusine residue to hypusine, completing the modification.
The hypusine residue in eIF5A plays a critical role in promoting the translation of specific mRNAs. It interacts with the ribosome and is believed to facilitate the movement of the ribosome along the mRNA during translation.
This modification is highly conserved across eukaryotic organisms, highlighting its crucial role in fundamental cellular processes. Its disruption can lead to cellular dysfunction and impaired growth.'
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Deoxyhypusine hydroxylase | A deoxyhypusine hydroxylase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9BU89] | Homo sapiens (human) |
| Deoxyhypusine synthase | A deoxyhypusine synthase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49366] | Homo sapiens (human) |
Compounds (7)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 2,2'-dipyridyl | 2,2'-bipyridine : A bipyridine in which the two pyridine moieties are linked by a bond between positions C-2 and C-2'. 2,2'-Dipyridyl: A reagent used for the determination of iron. | bipyridine | chelator; ferroptosis inhibitor |
| ciclopirox | cyclic hydroxamic acid; hydroxypyridone antifungal drug; pyridone | antibacterial agent; antiseborrheic | |
| deferiprone | deferiprone : A member of the class of 4-pyridones that is pyridin-4(1H)-one substituted at positions 1 and 2 by methyl groups and at position 3 by a hydroxy group. A lipid-soluble iron-chelator used for treatment of thalassaemia. Deferiprone: A pyridone derivative and iron chelator that is used in the treatment of IRON OVERLOAD in patients with THALASSEMIA. | 4-pyridones | iron chelator; protective agent |
| deferoxamine | Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form. desferrioxamine B : An acyclic desferrioxamine that is butanedioic acid in which one of the carboxy groups undergoes formal condensation with the primary amino group of N-(5-aminopentyl)-N-hydroxyacetamide and the second carboxy group undergoes formal condensation with the hydroxyamino group of N(1)-(5-aminopentyl)-N(1)-hydroxy-N(4)-[5-(hydroxyamino)pentyl]butanediamide. It is a siderophore native to Streptomyces pilosus biosynthesised by the DesABCD enzyme cluster as a high affinity Fe(III) chelator. | acyclic desferrioxamine | bacterial metabolite; ferroptosis inhibitor; iron chelator; siderophore |
| bosentan anhydrous | Bosentan: A sulfonamide and pyrimidine derivative that acts as a dual endothelin receptor antagonist used to manage PULMONARY HYPERTENSION and SYSTEMIC SCLEROSIS. | primary alcohol; pyrimidines; sulfonamide | antihypertensive agent; endothelin receptor antagonist |
| mimosine | L-mimosine : An L-alpha-amino acid that is propionic acid substituted by an amino group at position 2 and a 3-hydroxy-4-oxopyridin-1(4H)-yl group at position 3 (the 2S-stereoisomer). It a non-protein plant amino acid isolated from Mimosa pudica. | 4-pyridones; amino acid zwitterion; non-proteinogenic L-alpha-amino acid | EC 1.14.18.1 (tyrosinase) inhibitor; plant metabolite |
| n(1)-guanyl-1,7-diaminoheptane | 2-(7-aminoheptyl)guanidine : A member of the class of guanidines in which the imino hydrogen of guanidine itself has been replaced by a 7-aminoheptyl group. It is an inhibitor of deoxyhypusine synthase activity (GO:0034038). N(1)-guanyl-1,7-diaminoheptane: inhibits deoxyhypusine synthase | guanidines; primary amino compound | antineoplastic agent; EC 2.5.1.46 (deoxyhypusine synthase) inhibitor |