PDBsum entry 1lqk

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Protein chains
134 a.a. *
PO4 ×2
_MN ×2
__K ×2
Waters ×388
* Residue conservation analysis
PDB id:
Name: Transferase
Title: High resolution structure of fosfomycin resistance protein a (fosa)
Structure: Probable fosfomycin resistance protein. Chain: a, b. Synonym: fosa. Engineered: yes
Source: Pseudomonas aeruginosa. Organism_taxid: 287. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
1.35Å     R-factor:   0.138     R-free:   0.185
Authors: C.L.Rife,R.E.Pharris,M.E.Newcomer,R.N.Armstrong
Key ref: C.L.Rife et al. (2002). Crystal structure of a genomically encoded fosfomycin resistance protein (FosA) at 1.19 A resolution by MAD phasing off the L-III edge of Tl(+). J Am Chem Soc, 124, 11001-11003. PubMed id: 12224946 DOI: 10.1021/ja026879v
10-May-02     Release date:   11-Sep-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q9I4K6  (FOSA_PSEAE) -  Glutathione transferase FosA
135 a.a.
134 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
+ glutathione
= HX
+ R-S-glutathione
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     metabolic process   2 terms 
  Biochemical function     transferase activity     3 terms  


DOI no: 10.1021/ja026879v J Am Chem Soc 124:11001-11003 (2002)
PubMed id: 12224946  
Crystal structure of a genomically encoded fosfomycin resistance protein (FosA) at 1.19 A resolution by MAD phasing off the L-III edge of Tl(+).
C.L.Rife, R.E.Pharris, M.E.Newcomer, R.N.Armstrong.
The fosfomycin resistance protein (FosA) catalyzes the Mn(II)- and K+-dependent addition of glutathione to the oxirane of the antibiotic fosfomycin. The crystal structure of FosA from Pseudomonas aeruginosa was solved at a resolution of 1.19 A by multiwavelength anomalous diffraction at the L-III edge of a Tl+ derivative. The structure solution took advantage of the ability of Tl+ to substitute for K+. The existence of multiple Tl sites in the asymmetric unit suggests that this may be a generally useful technique for phasing protein crystal structures. A 1.35 A resolution structure with phosphate bound in the active site shows that the Mn(II) center has a rare four-coordinate geometry. The structure of the fosfomycin complex at 1.19 A resolution indicates that the Mn(II) center is close to five-coordinate with trigonal bipyramidal geometry and a ligand set consisting of two histidines (H7 and H64) and one phosphonate oxygen occupying the equatorial sites and the carboxylate of E110 at one of the apical sites. The oxirane oxygen of the substrate is located at the other apical site but is 0.2 A beyond the average Mn-O distance for five-coordinate Mn(II). The Mn(II) center is proposed to stabilize the alkoxide in the transition state, while the nearby hydroxyl group of T9 acts as a proton donor in the reaction. The K+ ion located 6.5 A from the Mn(II) appears to help orient the substrate for nucleophilic attack.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21392044 H.Xu, V.Miao, W.Kwong, R.Xia, and J.Davies (2011).
Identification of a novel fosfomycin resistance gene (fosA2) in Enterobacter cloacae from the Salmon River, Canada.
  Lett Appl Microbiol, 52, 427-429.  
20404116 J.Wachino, K.Yamane, S.Suzuki, K.Kimura, and Y.Arakawa (2010).
Prevalence of fosfomycin resistance among CTX-M-producing Escherichia coli clinical isolates in Japan and identification of novel plasmid-mediated fosfomycin-modifying enzymes.
  Antimicrob Agents Chemother, 54, 3061-3064.  
20822442 M.Morar, and G.D.Wright (2010).
The genomic enzymology of antibiotic resistance.
  Annu Rev Genet, 44, 25-51.  
19196010 D.W.Brown, M.R.Schaab, W.R.Birmingham, and R.N.Armstrong (2009).
Evolution of the antibiotic resistance protein, FosA, is linked to a catalytically promiscuous progenitor.
  Biochemistry, 48, 1847-1849.  
19016852 N.Allocati, L.Federici, M.Masulli, and C.Di Ilio (2009).
Glutathione transferases in bacteria.
  FEBS J, 276, 58-75.  
  19851000 P.D.Kiser, G.H.Lorimer, and K.Palczewski (2009).
Use of thallium to identify monovalent cation binding sites in GroEL.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 967-971.
PDB code: 3e76
18791196 I.Mulako, J.M.Farrant, H.Collett, and N.Illing (2008).
Expression of Xhdsi-1VOC, a novel member of the vicinal oxygen chelate (VOC) metalloenzyme superfamily, is up-regulated in leaves and roots during desiccation in the resurrection plant Xerophyta humilis (Bak) Dur and Schinz.
  J Exp Bot, 59, 3885-3901.  
18802628 T.Y.Zakharian, L.Di Costanzo, and D.W.Christianson (2008).
Synthesis of (2S)-2-amino-7,8-epoxyoctanoic acid and structure of its metal-bridging complex with human arginase I.
  Org Biomol Chem, 6, 3240-3243.
PDB code: 3dj8
17537395 R.E.Rigsby, D.W.Brown, E.Dawson, T.P.Lybrand, and R.N.Armstrong (2007).
A model for glutathione binding and activation in the fosfomycin resistance protein, FosA.
  Arch Biochem Biophys, 464, 277-283.  
15701635 S.Eschenburg, M.A.Priestman, F.A.Abdul-Latif, C.Delachaume, F.Fassy, and E.Schönbrunn (2005).
A novel inhibitor that suspends the induced fit mechanism of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA).
  J Biol Chem, 280, 14070-14075.
PDB code: 1ybg
15673790 S.R.Partridge, and R.M.Hall (2005).
Gene cassettes potentially encoding fosfomycin resistance determinants.
  Antimicrob Agents Chemother, 49, 860-861.  
15741169 Z.Beharry, and T.Palzkill (2005).
Functional analysis of active site residues of the fosfomycin resistance enzyme FosA from Pseudomonas aeruginosa.
  J Biol Chem, 280, 17786-17791.  
15075406 S.Pakhomova, C.L.Rife, R.N.Armstrong, and M.E.Newcomer (2004).
Structure of fosfomycin resistance protein FosA from transposon Tn2921.
  Protein Sci, 13, 1260-1265.
PDB code: 1npb
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.