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PDBsum entry 2qiv

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Transferase PDB id
2qiv
Jmol
Contents
Protein chain
262 a.a. *
Ligands
U21
Waters ×343
* Residue conservation analysis
PDB id:
2qiv
Name: Transferase
Title: Structural basis for the acyl chain selectivity and mechanism of udp-n-acetylglucosamine acyltransferase
Structure: Udp-n-acetylglucosamine acyltransferase. Chain: x. Synonym: acyl-[acyl-carrier-protein]--udp-n- acetylglucosamine o-acyltransferase. Engineered: yes
Source: Escherichia coli k12. Organism_taxid: 83333. Strain: k-12. Gene: lpxa. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.85Å     R-factor:   0.193     R-free:   0.221
Authors: A.H.Williams,C.R.H.Raetz
Key ref:
A.H.Williams and C.R.Raetz (2007). Structural basis for the acyl chain selectivity and mechanism of UDP-N-acetylglucosamine acyltransferase. Proc Natl Acad Sci U S A, 104, 13543-13550. PubMed id: 17698807 DOI: 10.1073/pnas.0705833104
Date:
05-Jul-07     Release date:   02-Oct-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0A722  (LPXA_ECOLI) -  Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase
Seq:
Struc:
262 a.a.
262 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.3.1.129  - Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (R)-3-hydroxytetradecanoyl-[acyl-carrier-protein] + UDP-N-acetyl-alpha-D- glucosamine = [acyl-carrier-protein] + UDP-3-O-(3-hydroxytetradecanoyl)- N-acetyl-alpha-D-glucosamine
(R)-3-hydroxytetradecanoyl-[acyl-carrier-protein]
+ UDP-N-acetyl-alpha-D- glucosamine
= [acyl-carrier-protein]
+ UDP-3-O-(3-hydroxytetradecanoyl)- N-acetyl-alpha-D-glucosamine
Bound ligand (Het Group name = U21)
matches with 92.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     lipid metabolic process   3 terms 
  Biochemical function     transferase activity     4 terms  

 

 
    Added reference    
 
 
DOI no: 10.1073/pnas.0705833104 Proc Natl Acad Sci U S A 104:13543-13550 (2007)
PubMed id: 17698807  
 
 
Structural basis for the acyl chain selectivity and mechanism of UDP-N-acetylglucosamine acyltransferase.
A.H.Williams, C.R.Raetz.
 
  ABSTRACT  
 
UDP-N-acetylglucosamine (UDP-GlcNAc) acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the reversible transfer of the R-3-hydroxyacyl chain from R-3-hydroxyacyl acyl carrier protein to the glucosamine 3-OH group of UDP-GlcNAc. Escherichia coli LpxA is highly selective for R-3-hydroxymyristate. The crystal structure of the E. coli LpxA homotrimer, determined previously in the absence of lipid substrates or products, revealed that LpxA contains an unusual, left-handed parallel beta-helix fold. We have now solved the crystal structures of E. coli LpxA with the bound product UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc at a resolution of 1.74 A and with bound UDP-3-O-(R-3-hydroxydecanoyl)-GlcNAc at 1.85 A. The structures of these complexes are consistent with the catalytic mechanism deduced by mutagenesis and with a recent 3.0-A structure of LpxA with bound UDP-GlcNAc. Our structures show how LpxA selects for 14-carbon R-3-hydroxyacyl chains and reveal two modes of UDP binding.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Functions of LpxA and LpxC in lipid A biosynthesis. LpxA catalyzes the first step, the acylation of UDP-GlcNAc (2, 4). This is a thermodynamically unfavorable reaction; therefore, LpxC catalyzes the committed step of the pathway (8).
Figure 2.
Fig. 2. Structural models of two LpxA/product complexes. (A) Side view of LpxA (ribbon diagram) with UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc (space filling model) at a resolution of 1.74 Å. Individual monomers of the LpxA homotrimer are colored green, magenta, and blue. The UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc product binds within the active site region located between adjacent subunits, as anticipated from site-directed mutagenesis studies (18). In the space-filling model of the ligand, carbon is yellow, nitrogen is blue, oxygen is red, and phosphorus is orange. (B) The top-down view demonstrates the threefold symmetry of the bound ligand. (C) The side view of LpxA (ribbon diagram) with bound UDP-3-O-(R-3-hydroxydecanoyl)-GlcNAc (space-filling model) at a resolution of 1.85 Å. The color scheme is similar to that described in A, except that the carbon atoms of the R-3-hydroxydecanoyl chain are gray. (D) Top-down view of the LpxA/UDP-3-O-(R-3-hydroxydecanoyl)-GlcNAc complex.
 
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23042606 L.E.Metzger, J.K.Lee, J.S.Finer-Moore, C.R.Raetz, and R.M.Stroud (2012).
LpxI structures reveal how a lipid A precursor is synthesized.
  Nat Struct Mol Biol, 19, 1132-1138.
PDB codes: 4ggi 4ggm 4j6e
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
20088879 D.Kenanov, C.Kaleta, A.Petzold, C.Hoischen, S.Diekmann, R.A.Siddiqui, and S.Schuster (2010).
Theoretical study of lipid biosynthesis in wild-type Escherichia coli and in a protoplast-type L-form using elementary flux mode analysis.
  FEBS J, 277, 1023-1034.  
19815028 X.Wang, and P.J.Quinn (2010).
Lipopolysaccharide: Biosynthetic pathway and structure modification.
  Prog Lipid Res, 49, 97.  
19655786 C.M.Bartling, and C.R.Raetz (2009).
Crystal structure and acyl chain selectivity of Escherichia coli LpxD, the N-acyltransferase of lipid A biosynthesis.
  Biochemistry, 48, 8672-8683.
PDB code: 3eh0
19501040 D.Hampel, C.J.Mau, and R.B.Croteau (2009).
Taxol biosynthesis: Identification and characterization of two acetyl CoA:taxoid-O-acetyl transferases that divert pathway flux away from Taxol production.
  Arch Biochem Biophys, 487, 91-97.  
19604481 J.H.Choi, B.C.May, C.Govaerts, and F.E.Cohen (2009).
Site-directed mutagenesis demonstrates the plasticity of the beta helix: implications for the structure of the misfolded prion protein.
  Structure, 17, 1014-1023.  
19456129 L.I.Robins, A.H.Williams, and C.R.Raetz (2009).
Structural basis for the sugar nucleotide and acyl-chain selectivity of Leptospira interrogans LpxA.
  Biochemistry, 48, 6191-6201.
PDB codes: 3hsq 3i3a 3i3x
19448740 M.Demendi, and C.Creuzenet (2009).
Cj1123c (PglD), a multifaceted acetyltransferase from Campylobacter jejuni.
  Biochem Cell Biol, 87, 469-483.  
18422345 C.M.Bartling, and C.R.Raetz (2008).
Steady-state kinetics and mechanism of LpxD, the N-acyltransferase of lipid A biosynthesis.
  Biochemistry, 47, 5290-5302.  
17956978 N.Zagorski, and C.R.Raetz (2007).
Profile of Christian R. H. Raetz.
  Proc Natl Acad Sci U S A, 104, 17252-17254.  
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.