Biology:UDP-3-O-acyl-N-acetylglucosamine deacetylase
From HandWiki
Short description: Type of enzyme
| UDP-3-O-acyl-N-acetylglucosamine deacetylase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 3.5.1.108 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
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UDP-3-O-acyl-N-acetylglucosamine deacetylase (EC 3.5.1.108), also known as LpxC, is a zinc-dependent enzyme involved in bacterial lipid A biosynthesis, catalyzing the removal of the acetyl group from UDP-3-O-acyl-N-acetylglucosamine, a key step in the production of lipopolysaccharides in the outer membrane of gram-negative bacteria.[1][2][3][4][5][6]
This enzyme catalyses the chemical reaction:
- UDP-3-O-[(3R)-3-hydroxymyristoyl]-N-acetylglucosamine + H2O UDP-3-O-[(3R)-3-hydroxymyristoyl]-D-glucosamine + acetate
Nomenclature
UDP-3-O-acyl-N-acetylglucosamine deacetylase is also known as:
- UDP-3-O-((3R)-3-hydroxymyristoyl)-N-acetylglucosamine amidohydrolase
- LpxC enzyme
- LpxC deacetylase
- deacetylase LpxC
- UDP-3-O-acyl-GlcNAc deacetylase
- UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase
- UDP-(3-O-acyl)-N-acetylglucosamine deacetylase
- UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase
- UDP-(3-O-(R-3-hydroxymyristoyl))-N-acetylglucosamine deacetylase)
Inhibitors
Various inhibitors of LpxC have been developed as potential antibiotics, though none have yet reached clinical trials.[7][8][9]
References
- ↑ "UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase functions through a general acid–base catalyst pair mechanism". The Journal of Biological Chemistry 280 (17): 16969–78. April 2005. doi:10.1074/jbc.M413560200. PMID 15705580.
- ↑ "UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase of Escherichia coli is a zinc metalloenzyme". Biochemistry 38 (6): 1902–11. February 1999. doi:10.1021/bi982339s. PMID 10026271.
- ↑ "Cloning, expression, and purification of UDP-3-O-acyl-GlcNAc deacetylase from Pseudomonas aeruginosa: a metalloamidase of the lipid A biosynthesis pathway". Journal of Bacteriology 179 (6): 2029–37. March 1997. doi:10.1128/jb.179.6.2029-2037.1997. PMID 9068651.
- ↑ "A fluorescence-based homogeneous assay for measuring activity of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase". Analytical Biochemistry 290 (2): 338–46. March 2001. doi:10.1006/abio.2000.4973. PMID 11237337.
- ↑ "Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis". Proceedings of the National Academy of Sciences of the United States of America 100 (14): 8146–50. July 2003. doi:10.1073/pnas.1432990100. PMID 12819349. Bibcode: 2003PNAS..100.8146W.
- ↑ "Crystal structure of LpxC from Pseudomonas aeruginosa complexed with the potent BB-78485 inhibitor". Protein Science 17 (3): 450–7. March 2008. doi:10.1110/ps.073324108. PMID 18287278.
- ↑ "Insights into the Zinc-Dependent Deacetylase LpxC: Biochemical Properties and Inhibitor Design". Current Topics in Medicinal Chemistry 16 (21): 2379–2430. 2016. doi:10.2174/1568026616666160413135835. PMID 27072691.
- ↑ "LpxC inhibitors: a patent review (2010-2016)". Expert Opinion on Therapeutic Patents 27 (11): 1227–1250. November 2017. doi:10.1080/13543776.2017.1360282. PMID 28742403.
- ↑ "Small molecule LpxC inhibitors against gram-negative bacteria: Advances and future perspectives". European Journal of Medicinal Chemistry 253. May 2023. doi:10.1016/j.ejmech.2023.115326. PMID 37023679.
- ↑ "Inhibitor Assessment against the LpxC Enzyme of Antibiotic-resistant Acinetobacter baumannii Using Virtual Screening, Dynamics Simulation, and in vitro Assays". Molecular Informatics 42 (2). February 2023. doi:10.1002/minf.202200061. PMID 36289054.
- ↑ "TP0586532, a non-hydroxamate LpxC inhibitor, has in vitro and in vivo antibacterial activities against Enterobacteriaceae". The Journal of Antibiotics 75 (2): 98–107. February 2022. doi:10.1038/s41429-021-00486-3. PMID 34837061.
External links
- UDP-3-O-acyl-N-acetylglucosamine+deacetylase at the US National Library of Medicine Medical Subject Headings (MeSH)
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