Biology:UDP-3-O-N-acetylglucosamine deacetylase
| UDP-3-O-acyl N-acetylglycosamine deacetylase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 crystal structure of aquifex aeolicus lpxc complexed with tu-514 | |||||||||
| Identifiers | |||||||||
| Symbol | LpxC | ||||||||
| Pfam | PF03331 | ||||||||
| Pfam clan | CL0329 | ||||||||
| InterPro | IPR004463 | ||||||||
| SCOP2 | 1nzt / SCOPe / SUPFAM | ||||||||
| CAZy | CE11 | ||||||||
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In molecular biology, UDP-3-O-N-acetylglucosamine deacetylase (also known as UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase or UDP-3-O-acyl-GlcNAc deacetylase), EC 3.5.1.-, is a bacterial enzyme involved in lipid A biosynthesis.
It is a zinc-dependent metalloamidase that catalyses the second and committed step in the biosynthesis of lipid A. Lipid A anchors lipopolysaccharide (the major constituent of the outer membrane) into the membrane in Gram negative bacteria. It shows no homology to mammalian metalloamidases and is essential for cell viability, making it an important target for the development of novel antibacterial compounds.[1] The structure of UDP-3-O-N-acetylglucosamine deacetylase (LpxC) from Aquifex aeolicus has a two-layer alpha/beta structure similar to that of the second domain of ribosomal protein S5, only in LpxC there is a duplication giving two structural repeats of this fold, each repeat being elaborated with additional structures forming the active site. LpxC contains a zinc-binding motif, which resides at the base of an active site cleft and adjacent to a hydrophobic tunnel occupied by a fatty acid.[2] This tunnel accounts for the specificity of LpxC toward substrates and inhibitors bearing appropriately positioned 3-O-fatty acid substituents.[3]
References
- ↑ "Refined solution structure of the LpxC-TU-514 complex and pKa analysis of an active site histidine: insights into the mechanism and inhibitor design". Biochemistry 44 (4): 1114–26. February 2005. doi:10.1021/bi047820z. PMID 15667205.
- ↑ "Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis". Proc. Natl. Acad. Sci. U.S.A. 100 (14): 8146–50. July 2003. doi:10.1073/pnas.1432990100. PMID 12819349. Bibcode: 2003PNAS..100.8146W.
- ↑ "Amphipathic benzoic acid derivatives: synthesis and binding in the hydrophobic tunnel of the zinc deacetylase LpxC". Bioorg. Med. Chem. 15 (7): 2617–23. April 2007. doi:10.1016/j.bmc.2007.01.044. PMID 17296300.
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