1xxe
From Proteopedia
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|PDB= 1xxe |SIZE=350|CAPTION= <scene name='initialview01'>1xxe</scene> | |PDB= 1xxe |SIZE=350|CAPTION= <scene name='initialview01'>1xxe</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=TUX:1,5-ANHYDRO-2-C-(CARBOXYMETHYL-N-HYDROXYAMIDE)-2-DEOXY-3-O-MYRISTOYL-D-GLUCITOL'>TUX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= LpxC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63363 Aquifex aeolicus]) | |GENE= LpxC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63363 Aquifex aeolicus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xxe OCA], [http://www.ebi.ac.uk/pdbsum/1xxe PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xxe RCSB]</span> | ||
}} | }} | ||
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[[Category: Rudolph, J.]] | [[Category: Rudolph, J.]] | ||
[[Category: Zhou, P.]] | [[Category: Zhou, P.]] | ||
| - | [[Category: | + | [[Category: lipid some]] |
| - | [[Category: | + | [[Category: lipopolysaccharide udp-3-o-acyl-n-acetylglucosamine deacetylase]] |
| - | + | [[Category: lp]] | |
| + | [[Category: lpxc]] | ||
| + | [[Category: metalloamidase]] | ||
| + | [[Category: tu-514]] | ||
| + | [[Category: zinc metalloamidase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:56:00 2008'' |
Revision as of 21:56, 30 March 2008
| |||||||
| Ligands: | , | ||||||
| Gene: | LpxC (Aquifex aeolicus) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
RDC refined solution structure of the AaLpxC/TU-514 complex
Overview
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.
About this Structure
1XXE is a Single protein structure of sequence from Aquifex aeolicus. This structure supersedes the now removed PDB entry 1NZT. Full crystallographic information is available from OCA.
Reference
Refined solution structure of the LpxC-TU-514 complex and pKa analysis of an active site histidine: insights into the mechanism and inhibitor design., Coggins BE, McClerren AL, Jiang L, Li X, Rudolph J, Hindsgaul O, Raetz CR, Zhou P, Biochemistry. 2005 Feb 1;44(4):1114-26. PMID:15667205
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