PDBsum entry 2ier

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
267 a.a. *
UDP ×2
PLM ×2
_ZN ×9
Waters ×77
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of aquifex aeolicus lpxc complexed with ur diphosphate
Structure: Udp-3-o-[3-hydroxymyristoyl] n-acetylglucosamine deacetylase. Chain: a, b. Synonym: udp-3-o-acyl-glcnac deacetylase. Engineered: yes. Mutation: yes
Source: Aquifex aeolicus. Organism_taxid: 63363. Gene: lpxc. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.70Å     R-factor:   0.213     R-free:   0.241
Authors: H.A.Gennadios,D.W.Christianson
Key ref:
H.A.Gennadios and D.W.Christianson (2006). Binding of uridine 5'-diphosphate in the "basic patch" of the zinc deacetylase LpxC and implications for substrate binding. Biochemistry, 45, 15216-15223. PubMed id: 17176043 DOI: 10.1021/bi0619021
19-Sep-06     Release date:   09-Jan-07    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O67648  (LPXC_AQUAE) -  UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase
282 a.a.
267 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     lipid metabolic process   2 terms 
  Biochemical function     hydrolase activity     2 terms  


DOI no: 10.1021/bi0619021 Biochemistry 45:15216-15223 (2006)
PubMed id: 17176043  
Binding of uridine 5'-diphosphate in the "basic patch" of the zinc deacetylase LpxC and implications for substrate binding.
H.A.Gennadios, D.W.Christianson.
LpxC is a zinc metalloenzyme that catalyzes the first committed step in the biosynthesis of lipid A, a vital component of the outer membrane of Gram-negative bacteria. Accordingly, the inhibition of LpxC is an attractive strategy for the treatment of Gram-negative bacterial infections. Here, we report the 2.7 A resolution X-ray crystal structure of LpxC from Aquifex aeolicus complexed with uridine 5'-diphosphate (UDP), and the 3.1 A resolution structure of LpxC complexed with pyrophosphate. The X-ray crystal structure of the LpxC-UDP complex provides the first view of interactions likely to be exploited by the substrate UDP group in the "basic patch" of the active site. The diphosphate group of UDP makes hydrogen bond interactions with strictly conserved residue K239 as well as solvent molecules. The ribose moiety of UDP interacts with partially conserved residue E197. The UDP uracil group hydrogen bonds with both the backbone NH group and the backbone carbonyl group of E160, and with the backbone NH group of K162 through an intervening water molecule. Finally, the alpha-phosphate and uracil groups of UDP interact with R143 and R262 through intervening water molecules. The structure of LpxC complexed with pyrophosphate reveals generally similar intermolecular interactions in the basic patch. Unexpectedly, diphosphate binding in both complexes is accompanied by coordination to an additional zinc ion, resulting in the identification of a new metal-binding site termed the E-site. The structures of the LpxC-UDP and LpxC-pyrophosphate complexes provide new insights with regard to substrate recognition in the basic patch and metal ion coordination in the active site of LpxC.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21167751 C.J.Lee, X.Liang, X.Chen, D.Zeng, S.H.Joo, H.S.Chung, A.W.Barb, S.M.Swanson, R.A.Nicholas, Y.Li, E.J.Toone, C.R.Raetz, and P.Zhou (2011).
Species-specific and inhibitor-dependent conformations of LpxC: implications for antibiotic design.
  Chem Biol, 18, 38-47.
PDB codes: 3p3c 3p3e 3p3g
20136146 M.Hernick, S.G.Gattis, J.E.Penner-Hahn, and C.A.Fierke (2010).
Activation of Escherichia coli UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase by Fe2+ yields a more efficient enzyme with altered ligand affinity.
  Biochemistry, 49, 2246-2255.  
19256534 A.W.Barb, T.M.Leavy, L.I.Robins, Z.Guan, D.A.Six, P.Zhou, M.J.Hangauer, C.R.Bertozzi, and C.R.Raetz (2009).
Uridine-based inhibitors as new leads for antibiotics targeting Escherichia coli LpxC.
  Biochemistry, 48, 3068-3077.  
18287278 I.Mochalkin, J.D.Knafels, and S.Lightle (2008).
Crystal structure of LpxC from Pseudomonas aeruginosa complexed with the potent BB-78485 inhibitor.
  Protein Sci, 17, 450-457.
PDB code: 2ves
18025458 A.W.Barb, L.Jiang, C.R.Raetz, and P.Zhou (2007).
Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: Time-dependent inhibition and specificity in ligand binding.
  Proc Natl Acad Sci U S A, 104, 18433-18438.
PDB code: 2jt2
17362200 C.R.Raetz, C.M.Reynolds, M.S.Trent, and R.E.Bishop (2007).
Lipid A modification systems in gram-negative bacteria.
  Annu Rev Biochem, 76, 295-329.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.