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Isomerase PDB id
2i2w
Jmol
Contents
Protein chains
192 a.a. *
177 a.a. *
Ligands
GOL
Waters ×618
* Residue conservation analysis
PDB id:
2i2w
Name: Isomerase
Title: Crystal structure of escherichia coli phosphoheptose isomera
Structure: Phosphoheptose isomerase. Chain: a, b, c, d. Synonym: sedoheptulose 7-phosphate isomerase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: gmha, lpca, tfra, b0222. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.95Å     R-factor:   0.172     R-free:   0.219
Authors: G.Deleon,K.Blakely,K.Zhang,G.Wright,M.Junop
Key ref:
P.L.Taylor et al. (2008). Structure and Function of Sedoheptulose-7-phosphate Isomerase, a Critical Enzyme for Lipopolysaccharide Biosynthesis and a Target for Antibiotic Adjuvants. J Biol Chem, 283, 2835-2845. PubMed id: 18056714 DOI: 10.1074/jbc.M706163200
Date:
17-Aug-06     Release date:   21-Aug-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P63224  (GMHA_ECOLI) -  Phosphoheptose isomerase
Seq:
Struc: 		192 a.a.
192 a.a.
Protein chains
Pfam   ArchSchema ?
P63224  (GMHA_ECOLI) -  Phosphoheptose isomerase
Seq:
Struc: 		192 a.a.
177 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: E.C.5.3.1.28  - D-sedoheptulose 7-phosphate isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: D-sedoheptulose 7-phosphate = D-glycero-D-manno-heptose 7-phosphate
D-sedoheptulose 7-phosphate
 = D-glycero-D-manno-heptose 7-phosphate
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     carbohydrate metabolic process   3 terms 
  Biochemical function     isomerase activity     4 terms  

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.M706163200 J Biol Chem 283:2835-2845 (2008)
PubMed id: 18056714  
 
 
Structure and Function of Sedoheptulose-7-phosphate Isomerase, a Critical Enzyme for Lipopolysaccharide Biosynthesis and a Target for Antibiotic Adjuvants.
P.L.Taylor, K.M.Blakely, G.P.de Leon, J.R.Walker, F.McArthur, E.Evdokimova, K.Zhang, M.A.Valvano, G.D.Wright, M.S.Junop.
 
  ABSTRACT  
 
The barrier imposed by lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria presents a significant challenge in treatment of these organisms with otherwise effective hydrophobic antibiotics. The absence of l-glycero-d-manno-heptose in the LPS molecule is associated with a dramatically increased bacterial susceptibility to hydrophobic antibiotics and thus enzymes in the ADP-heptose biosynthesis pathway are of significant interest. GmhA catalyzes the isomerization of d-sedoheptulose 7-phosphate into d-glycero-d-manno-heptose 7-phosphate, the first committed step in the formation of ADP-heptose. Here we report structures of GmhA from Escherichia coli and Pseudomonas aeruginosa in apo, substrate, and product-bound forms, which together suggest that GmhA adopts two distinct conformations during isomerization through reorganization of quaternary structure. Biochemical characterization of GmhA mutants, combined with in vivo analysis of LPS biosynthesis and novobiocin susceptibility, identifies key catalytic residues. We postulate GmhA acts through an enediol-intermediate isomerase mechanism.
 
  Selected figure(s)  
 
Figure 1.
FIGURE 1. LPS structure and activity of GmhA. A, general structure of LPS in Gram-negative bacteria. Kdo, 3-deoxy-D-manno-oct-2-ulosonic acid; Hep, heptose; P, phosphate. B, schematic of the isomerase reaction catalyzed by GmhA, where D-sedoheptulose 7-phosphate is converted into D-glycero-D-manno-heptose 7-phosphate. 		Figure 8.
FIGURE 8. Proposed mechanism of GmhA. The GmhA catalyzed conversion of D-sedoheptulose 7-phosphate into D-glycero-D-manno-heptose 7-phosphate is predicted to proceed through an enediol intermediate, where Glu-65 serves as the catalytic base and His-180 serves as the catalytic acid.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 2835-2845) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20581202 A.Daddaoua, T.Krell, C.Alfonso, B.Morel, and J.L.Ramos (2010).
Compartmentalized glucose metabolism in Pseudomonas putida is controlled by the PtxS repressor.
  J Bacteriol, 192, 4357-4366.  
20877901 L.Cipolla, L.Gabrielli, D.Bini, L.Russo, and N.Shaikh (2010).
Kdo: a critical monosaccharide for bacteria viability.
  Nat Prod Rep, 27, 1618-1629.  
20954237 L.J.Gourlay, S.Sommaruga, M.Nardini, P.Sperandeo, G.Dehò, A.Polissi, and M.Bolognesi (2010).
Probing the active site of the sugar isomerase domain from E. coli arabinose-5-phosphate isomerase via X-ray crystallography.
  Protein Sci, 19, 2430-2439.
PDB code: 2xhz
21572503 U.Amineni, D.Pradhan, and H.Marisetty (2010).
In silico identification of common putative drug targets in Leptospira interrogans.
  J Chem Biol, 3, 165-173.  
19506074 A.Daddaoua, T.Krell, and J.L.Ramos (2009).
Regulation of glucose metabolism in Pseudomonas: the phosphorylative branch and entner-doudoroff enzymes are regulated by a repressor containing a sugar isomerase domain.
  J Biol Chem, 284, 21360-21368.  
19006597 P.L.Taylor, and G.D.Wright (2008).
Novel approaches to discovery of antibacterial agents.
  Anim Health Res Rev, 9, 237-246.  
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 code is shown on the right.