| Structural highlights
4wh2 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | 4ocj, 4ock, 4oco, 4ocp, 4ocq, 4ocu, 4ocv, 4wh1 |
| Activity: | N-acetylhexosamine 1-kinase, with EC number 2.7.1.162 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[NAHK_BIFL2] Phosphorylates both N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) at similar rates. Involved in the lacto-N-biose I/galacto-N-biose (LNB/GNB) degradation pathway, which is important for host intestinal colonization by bifidobacteria. Also accepts GTP and ITP as phosphate donors. In vitro, can phosphorylate several GlcNAc and GalNAc derivatives.[1] [2] [3]
Publication Abstract from PubMed
Infant gut-associated bifidobacteria possess a metabolic pathway to utilize lacto-N-biose (Gal-beta1,3-GlcNAc) and galacto-N-biose (Gal-beta1,3-GalNAc) from human milk and glycoconjugates specifically. In this pathway, N-acetylhexosamine 1-kinase (NahK) catalyzes the phosphorylation of GlcNAc or GalNAc at the anomeric C1 position with ATP. Crystal structures of NahK have only been determined in the closed state. In this study, we determined open state structures of NahK in three different forms (apo, ADP complex, and ATP complex). A comparison of the open and closed state structures revealed an induced fit structural change defined by two rigid domains. ATP binds to the small N-terminal domain, and binding of the N-acetylhexosamine substrate to the large C-terminal domain induces a closing conformational change with a rotation angle of 16 degrees . In the nucleotide binding site, two magnesium ions bridging the alpha-gamma and beta-gamma phosphates were identified. A mutational analysis indicated that a residue coordinating both of the two magnesium ions (Asp228) is essential for catalysis. The involvement of two magnesium ions in the catalytic machinery is structurally similar to the catalytic structures of protein kinases and aminoglycoside phosphotransferases, but distinct from the structures of other anomeric kinases or sugar 6-kinases. These findings help to elucidate the possible evolutionary adaptation of substrate specificities and induced fit mechanism.
Open-close structural change upon ligand binding and two magnesium ions required for the catalysis of N-acetylhexosamine 1-kinase.,Sato M, Arakawa T, Nam YW, Nishimoto M, Kitaoka M, Fushinobu S Biochim Biophys Acta. 2015 Jan 30;1854(5):333-340. doi:, 10.1016/j.bbapap.2015.01.011. PMID:25644306[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nishimoto M, Kitaoka M. Identification of N-acetylhexosamine 1-kinase in the complete lacto-N-biose I/galacto-N-biose metabolic pathway in Bifidobacterium longum. Appl Environ Microbiol. 2007 Oct;73(20):6444-9. Epub 2007 Aug 24. PMID:17720833 doi:http://dx.doi.org/10.1128/AEM.01425-07
- ↑ Cai L, Guan W, Kitaoka M, Shen J, Xia C, Chen W, Wang PG. A chemoenzymatic route to N-acetylglucosamine-1-phosphate analogues: substrate specificity investigations of N-acetylhexosamine 1-kinase. Chem Commun (Camb). 2009 May 28;(20):2944-6. doi: 10.1039/b904853g. Epub 2009 Apr, 24. PMID:19436918 doi:http://dx.doi.org/10.1039/b904853g
- ↑ Cai L, Guan W, Wang W, Zhao W, Kitaoka M, Shen J, O'Neil C, Wang PG. Substrate specificity of N-acetylhexosamine kinase towards N-acetylgalactosamine derivatives. Bioorg Med Chem Lett. 2009 Sep 15;19(18):5433-5. doi: 10.1016/j.bmcl.2009.07.104., Epub 2009 Jul 25. PMID:19683921 doi:http://dx.doi.org/10.1016/j.bmcl.2009.07.104
- ↑ Sato M, Arakawa T, Nam YW, Nishimoto M, Kitaoka M, Fushinobu S. Open-close structural change upon ligand binding and two magnesium ions required for the catalysis of N-acetylhexosamine 1-kinase. Biochim Biophys Acta. 2015 Jan 30;1854(5):333-340. doi:, 10.1016/j.bbapap.2015.01.011. PMID:25644306 doi:http://dx.doi.org/10.1016/j.bbapap.2015.01.011
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