Enzymes
| UniProtKB help_outline | 5 proteins |
| GO Molecular Function help_outline |
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Reaction participants Show >> << Hide
- Name help_outline ATP Identifier CHEBI:30616 (Beilstein: 3581767) help_outline Charge -4 Formula C10H12N5O13P3 InChIKeyhelp_outline ZKHQWZAMYRWXGA-KQYNXXCUSA-J SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,256 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline N-acetyl-D-muramoyl-L-alanyl-D-isoglutamine Identifier CHEBI:155830 Charge -1 Formula C19H31N4O11 InChIKeyhelp_outline BSOQXXWZTUDTEL-QAQREVAFSA-M SMILEShelp_outline O[C@H]1[C@@H]([C@H](C(O[C@@H]1CO)O)NC(=O)C)O[C@H](C)C(=O)N[C@H](C(=O)N[C@H](CCC(=O)[O-])C(=O)N)C 2D coordinates Mol file for the small molecule Search links Involved in 4 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 6-O-phospho-N-acetyl-D-muramoyl-L-alanyl-D-isoglutamine Identifier CHEBI:194492 Charge -3 Formula C19H30N4O14P InChIKeyhelp_outline BUFVUXUWHKVIRE-QAQREVAFSA-K SMILEShelp_outline O[C@H]1[C@@H]([C@H](C(O[C@@H]1COP(=O)([O-])[O-])O)NC(=O)C)O[C@H](C)C(=O)N[C@H](C(=O)N[C@H](CCC(=O)[O-])C(=O)N)C 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
- Name help_outline ADP Identifier CHEBI:456216 (Beilstein: 3783669) help_outline Charge -3 Formula C10H12N5O10P2 InChIKeyhelp_outline XTWYTFMLZFPYCI-KQYNXXCUSA-K SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 835 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:75935 | RHEA:75936 | RHEA:75937 | RHEA:75938 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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| Gene Ontology help_outline |
Publications
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Phosphorylation of muramyl peptides by NAGK is required for NOD2 activation.
Stafford C.A., Gassauer A.M., de Oliveira Mann C.C., Tanzer M.C., Fessler E., Wefers B., Nagl D., Kuut G., Sulek K., Vasilopoulou C., Schwojer S.J., Wiest A., Pfautsch M.K., Wurst W., Yabal M., Froehlich T., Mann M., Gisch N., Jae L.T., Hornung V.
Bacterial cell wall components provide various unique molecular structures that are detected by pattern recognition receptors (PRRs) of the innate immune system as non-self. Most bacterial species form a cell wall that consists of peptidoglycan (PGN), a polymeric structure comprising alternating a ... >> More
Bacterial cell wall components provide various unique molecular structures that are detected by pattern recognition receptors (PRRs) of the innate immune system as non-self. Most bacterial species form a cell wall that consists of peptidoglycan (PGN), a polymeric structure comprising alternating amino sugars that form strands cross-linked by short peptides. Muramyl dipeptide (MDP) has been well documented as a minimal immunogenic component of peptidoglycan<sup>1-3</sup>. MDP is sensed by the cytosolic nucleotide-binding oligomerization domain-containing protein 2<sup>4</sup> (NOD2). Upon engagement, it triggers pro-inflammatory gene expression, and this functionality is of critical importance in maintaining a healthy intestinal barrier function<sup>5</sup>. Here, using a forward genetic screen to identify factors required for MDP detection, we identified N-acetylglucosamine kinase (NAGK) as being essential for the immunostimulatory activity of MDP. NAGK is broadly expressed in immune cells and has previously been described to contribute to the hexosamine biosynthetic salvage pathway<sup>6</sup>. Mechanistically, NAGK functions upstream of NOD2 by directly phosphorylating the N-acetylmuramic acid moiety of MDP at the hydroxyl group of its C6 position, yielding 6-O-phospho-MDP. NAGK-phosphorylated MDP-but not unmodified MDP-constitutes an agonist for NOD2. Macrophages from mice deficient in NAGK are completely deficient in MDP sensing. These results reveal a link between amino sugar metabolism and innate immunity to bacterial cell walls. << Less
Nature 609:590-596(2022) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.