PDBsum entry 1ez2

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
329 a.a. *
DII ×2
_ZN ×4
Waters ×286
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Three-dimensional structure of the zinc-containing phosphotriesterase with bound substrate analog diisopropylmethyl phosphonate.
Structure: Phosphotriesterase. Chain: a, b. Synonym: parathion hydrolase, pte. Engineered: yes
Source: Brevundimonas diminuta. Organism_taxid: 293. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
1.90Å     R-factor:   0.183    
Authors: H.M.Holden,M.M.Benning,F.M.Raushel,S.-B.Hong
Key ref:
M.M.Benning et al. (2000). The binding of substrate analogs to phosphotriesterase. J Biol Chem, 275, 30556-30560. PubMed id: 10871616 DOI: 10.1074/jbc.M003852200
09-May-00     Release date:   20-Dec-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0A434  (OPD_BREDI) -  Parathion hydrolase
365 a.a.
329 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Aryldialkylphosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An aryl dialkyl phosphate + H2O = dialkyl phosphate + an aryl alcohol
aryl dialkyl phosphate
+ H(2)O
= dialkyl phosphate
+ aryl alcohol
      Cofactor: Divalent cation
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     catabolic process   2 terms 
  Biochemical function     hydrolase activity     5 terms  


    Added reference    
DOI no: 10.1074/jbc.M003852200 J Biol Chem 275:30556-30560 (2000)
PubMed id: 10871616  
The binding of substrate analogs to phosphotriesterase.
M.M.Benning, S.B.Hong, F.M.Raushel, H.M.Holden.
Phosphotriesterase (PTE) from Pseudomonas diminuta catalyzes the detoxification of organophosphates such as the widely utilized insecticide paraoxon and the chemical warfare agent sarin. The three-dimensional structure of the enzyme is known from high resolution x-ray crystallographic analyses. Each subunit of the homodimer folds into a so-called TIM barrel, with eight strands of parallel beta-sheet. The two zinc ions required for activity are positioned at the C-terminal portion of the beta-barrel. Here, we describe the three-dimensional structure of PTE complexed with the inhibitor diisopropyl methyl phosphonate, which serves as a mimic for sarin. Additionally, the structure of the enzyme complexed with triethyl phosphate is also presented. In the case of the PTE-diisopropyl methyl phosphonate complex, the phosphoryl oxygen of the inhibitor coordinates to the more solvent-exposed zinc ion (2.5 A), thereby lending support to the presumed catalytic mechanism involving metal coordination of the substrate. In the PTE-triethyl phosphate complex, the phosphoryl oxygen of the inhibitor is positioned at 3.4 A from the more solvent-exposed zinc ion. The two structures described in this report provide additional molecular understanding for the ability of this remarkable enzyme to hydrolyze such a wide range of organophosphorus substrates.
  Selected figure(s)  
Figure 4.
Fig. 4. Binding pocket for the triethyl phosphate inhibitor. Those amino acid residues positioned at approximately 5.0 Å of the ligand are included in this stereo representation of the PTE active site. The ligand is highlighted in yellow bonds.
Figure 5.
Fig. 5. Superposition of the three inhibitors bound in the PTE active site. The diethyl 4-methylbenzylphosphonate, diisopropyl methyl phosphonate, and triethyl phosphate ligands are shown in red, blue, and green, respectively.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 30556-30560) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21037279 L.Briseño-Roa, C.M.Timperley, A.D.Griffiths, and A.R.Fersht (2011).
Phosphotriesterase variants with high methylphosphonatase activity and strong negative trade-off against phosphotriesters.
  Protein Eng Des Sel, 24, 151-159.  
21362400 M.Latorre, F.Olivares, A.Reyes-Jara, G.López, and M.González (2011).
CutC is induced late during copper exposure and can modify intracellular copper content in Enterococcus faecalis.
  Biochem Biophys Res Commun, 406, 633-637.  
19938866 D.E.Gomes, R.D.Lins, P.G.Pascutti, C.Lei, and T.A.Soares (2010).
The role of nonbonded interactions in the conformational dynamics of organophosphorous hydrolase adsorbed onto functionalized mesoporous silica surfaces.
  J Phys Chem B, 114, 531-540.  
19353598 X.Zhang, R.Wu, L.Song, Y.Lin, M.Lin, Z.Cao, W.Wu, and Y.Mo (2009).
Molecular dynamics simulations of the detoxification of paraoxon catalyzed by phosphotriesterase.
  J Comput Chem, 30, 2388-2401.  
19635449 Z.Li, F.Song, Z.Zhuang, D.Dunaway-Mariano, and K.S.Anderson (2009).
Monitoring enzyme catalysis in the multimeric state: direct observation of Arthrobacter 4-hydroxybenzoyl-coenzyme A thioesterase catalytic complexes using time-resolved electrospray ionization mass spectrometry.
  Anal Biochem, 394, 209-216.  
18274677 M.Jarenmark, S.Kappen, M.Haukka, and E.Nordlander (2008).
Symmetrical and unsymmetrical dizinc complexes as models for the active sites of hydrolytic enzymes.
  Dalton Trans, (), 993-996.  
18535849 R.E.Mirams, S.J.Smith, K.S.Hadler, D.L.Ollis, G.Schenk, and L.R.Gahan (2008).
Cadmium(II) complexes of the glycerophosphodiester-degrading enzyme GpdQ and a biomimetic N,O ligand.
  J Biol Inorg Chem, 13, 1065-1072.  
19051105 S.Yair, B.Ofer, E.Arik, S.Shai, R.Yossi, D.Tzvika, and K.Amir (2008).
Organophosphate degrading microorganisms and enzymes as biocatalysts in environmental and personal decontamination applications.
  Crit Rev Biotechnol, 28, 265-275.  
17575004 H.Jiang, C.Yang, H.Qu, Z.Liu, Q.S.Fu, and C.Qiao (2007).
Cloning of a novel aldo-keto reductase gene from Klebsiella sp. strain F51-1-2 and its functional expression in Escherichia coli.
  Appl Environ Microbiol, 73, 4959-4965.  
16734778 I.Horne, X.Qiu, D.L.Ollis, R.J.Russell, and J.G.Oakeshott (2006).
Functional effects of amino acid substitutions within the large binding pocket of the phosphotriesterase OpdA from Agrobacterium sp. P230.
  FEMS Microbiol Lett, 259, 187-194.  
15909078 L.Merone, L.Mandrich, M.Rossi, and G.Manco (2005).
A thermostable phosphotriesterase from the archaeon Sulfolobus solfataricus: cloning, overexpression and properties.
  Extremophiles, 9, 297-305.  
12505981 A.D.Griffiths, and D.S.Tawfik (2003).
Directed evolution of an extremely fast phosphotriesterase by in vitro compartmentalization.
  EMBO J, 22, 24-35.  
12548728 J.Koca, C.G.Zhan, R.C.Rittenhouse, and R.L.Ornstein (2003).
Coordination number of zinc ions in the phosphotriesterase active site by molecular dynamics and quantum mechanics.
  J Comput Chem, 24, 368-378.  
11916726 C.M.Cho, A.Mulchandani, and W.Chen (2002).
Bacterial cell surface display of organophosphorus hydrolase for selective screening of improved hydrolysis of organophosphate nerve agents.
  Appl Environ Microbiol, 68, 2026-2030.  
12057683 F.M.Raushel (2002).
Bacterial detoxification of organophosphate nerve agents.
  Curr Opin Microbiol, 5, 288-295.  
11258882 M.M.Benning, H.Shim, F.M.Raushel, and H.M.Holden (2001).
High resolution X-ray structures of different metal-substituted forms of phosphotriesterase from Pseudomonas diminuta.
  Biochemistry, 40, 2712-2722.
PDB codes: 1hzy 1i03 1i0b 1i0d 1jgm
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.