Enzymes
| UniProtKB help_outline | 8 proteins |
Reaction participants Show >> << Hide
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Namehelp_outline
N6-isonicotinyl-L-lysyl-[protein]
Identifier
RHEA-COMP:20155
Reactive part
help_outline
- Name help_outline N6-isonicotinyl-L-lysine residue Identifier CHEBI:233146 Charge 0 Formula C12H15N3O2 SMILEShelp_outline N(CCCC[C@@H](C(*)=O)N*)C(C=1C=CN=CC1)=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,648 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline isonicotinate Identifier CHEBI:38186 Charge -1 Formula C6H4NO2 InChIKeyhelp_outline TWBYWOBDOCUKOW-UHFFFAOYSA-M SMILEShelp_outline C(=O)(C=1C=CN=CC1)[O-] 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
L-lysyl-[protein]
Identifier
RHEA-COMP:9752
Reactive part
help_outline
- Name help_outline L-lysine residue Identifier CHEBI:29969 Charge 1 Formula C6H13N2O SMILEShelp_outline C([C@@H](C(*)=O)N*)CCC[NH3+] 2D coordinates Mol file for the small molecule Search links Involved in 153 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:83543 | RHEA:83544 | RHEA:83545 | RHEA:83546 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Related reactions help_outline
More general form(s) of this reaction
Publications
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Isonicotinylation is a histone mark induced by the anti-tuberculosis first-line drug isoniazid.
Jiang Y., Li Y., Liu C., Zhang L., Lv D., Weng Y., Cheng Z., Chen X., Zhan J., Zhang H.
Isoniazid (INH) is a first-line anti-tuberculosis drug used for nearly 70 years. However, the mechanism underlying the side effects of INH has remained elusive. Here, we report that INH and its metabolites induce a post-translational modification (PTM) of histones, lysine isonicotinylation (K<sub> ... >> More
Isoniazid (INH) is a first-line anti-tuberculosis drug used for nearly 70 years. However, the mechanism underlying the side effects of INH has remained elusive. Here, we report that INH and its metabolites induce a post-translational modification (PTM) of histones, lysine isonicotinylation (K<sub>inic</sub>), also called 4-picolinylation, in cells and mice. INH promotes the biosynthesis of isonicotinyl-CoA (Inic-CoA), a co-factor of intracellular isonicotinylation. Mass spectrometry reveals 26 K<sub>inic</sub> sites in histones in HepG2 cells. Acetyltransferases CREB-binding protein (CBP) and P300 catalyse histone K<sub>inic</sub>, while histone deacetylase HDAC3 functions as a deisonicotinylase. Notably, MNase sensitivity assay and RNA-seq analysis show that histone K<sub>inic</sub> relaxes chromatin structure and promotes gene transcription. INH-mediated histone K<sub>inic</sub> upregulates PIK3R1 gene expression and activates the PI3K/Akt/mTOR signalling pathway in liver cancer cells, linking INH to tumourigenicity in the liver. We demonstrate that K<sub>inic</sub> is a histone acylation mark with a pyridine ring, which may have broad biological effects. Therefore, INH-induced isonicotinylation potentially accounts for the side effects in patients taking INH long-term for anti-tuberculosis therapy, and this modification may increase the risk of cancer in humans. << Less
Nat. Commun. 12:5548-5548(2021) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.