Summary for 1XXE
| Entry DOI | 10.2210/pdb1xxe/pdb |
| Descriptor | UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase, ZINC ION, 1,5-ANHYDRO-2-C-(CARBOXYMETHYL-N-HYDROXYAMIDE)-2-DEOXY-3-O-MYRISTOYL-D-GLUCITOL (3 entities in total) |
| Functional Keywords | lpxc; tu-514; lps; lipid a; lipopolysaccharide udp-3-o-acyl-n-acetylglucosamine deacetylase; metalloamidase; zinc metalloamidase, hydrolase |
| Biological source | Aquifex aeolicus |
| Total number of polymer chains | 1 |
| Total formula weight | 32690.89 |
| Authors | Coggins, B.E.,McClerren, A.L.,Jiang, L.,Li, X.,Rudolph, J.,Hindsgaul, O.,Raetz, C.R.H.,Zhou, P. (deposition date: 2004-11-04, release date: 2004-11-23, Last modification date: 2024-05-22) |
| Primary citation | Coggins, B.E.,McClerren, A.L.,Jiang, L.,Li, X.,Rudolph, J.,Hindsgaul, O.,Raetz, C.R.H.,Zhou, P. Refined Solution Structure of the LpxC-TU-514 Complex and pK(a) Analysis of an Active Site Histidine: Insights into the Mechanism and Inhibitor Design Biochemistry, 44:1114-1126, 2005 Cited by PubMed Abstract: Lipopolysaccharide, the major constituent of the outer monolayer of the outer membrane of Gram-negative bacteria, is anchored into the membrane through the hydrophobic moiety lipid A, a hexaacylated disaccharide. The zinc-dependent metalloamidase UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) catalyzes the second and committed step in the biosynthesis of lipid A. LpxC shows no homology to mammalian metalloamidases and is essential for cell viability, making it an important target for the development of novel antibacterial compounds. Recent NMR and X-ray studies of the LpxC from Aquifex aeolicus have provided the first structural information about this family of proteins. Insight into the catalytic mechanism and the design of effective inhibitors could be facilitated by more detailed structural and biochemical studies that define substrate-protein interactions and the roles of specific residues in the active site. Here, we report the synthesis of the (13)C-labeled substrate-analogue inhibitor TU-514, and the subsequent refinement of the solution structure of the A. aeolicus LpxC-TU-514 complex using residual dipolar couplings. We also reevaluate the catalytic role of an active site histidine, H253, on the basis of both its pK(a) as determined by NMR titration and pH-dependent kinetic analyses. These results provide a structural basis for the design of more potent LpxC inhibitors than those that are currently available. PubMed: 15667205DOI: 10.1021/bi047820z PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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