Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.1.8.2 extracted from

  • Xu, C.; Yang, L.; Yu, J.; Liao, R.
    What roles do the residue Asp229 and the coordination variation of calcium play of the reaction mechanism of the diisopropyl-fluorophosphatase? A DFT investigation (2016), Theoret. Chem. Accounts, 135, 1-11.
No PubMed abstract available
Search for more literature for 3.1.8.2

Protein Variants

Protein Variants Comment Organism
Asp229/Asn120 site-directed mutagenesis, the mutant shows impaired catalytic activity or decreased substrate binding affinity Loligo vulgaris
Asp229/Asn175 site-directed mutagenesis, the mutant shows impaired catalytic activity or decreased substrate binding affinity Loligo vulgaris
Glu21/Asn120 site-directed mutagenesis, the mutant shows impaired catalytic activity or decreased substrate binding affinity Loligo vulgaris
Glu21/Asn175 site-directed mutagenesis, the mutant shows impaired catalytic activity or decreased substrate binding affinity Loligo vulgaris
additional information the kinetic measurements of enzyme mutants show that the double mutants Glu21/Asn120, Glu21/Asn175, Asp229/Asn120, and Asp229/Asn175 have impaired catalytic activity or decreased substrate binding affinity although their structures provide unchanged calcium coordination environment proving signification of suitable electrostatic effect of the active site for binding and catalysis Loligo vulgaris

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ required, Ca2+ ion in active site, coordinated to the moiety of DFP, two glutamines (Asn120 and Asn175), two negatively charged residues (Asp229 and Glu21), and two water molecules, thus completes its hepta-coordinated. Therefore, the metal ion plays an essential role in the precise orientation and activation of the substrate. The active site solvent molecule coordinating the catalytic calcium ion is identified as a water molecule other than a hydroxide Loligo vulgaris

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
diisopropyl fluorophosphate + H2O Loligo vulgaris
-
 diisopropyl phosphate + fluoride
-
 ?

Organism

Organism UniProt Comment Textmining
Loligo vulgaris Q7SIG4
-
-

Reaction

Reaction Comment Organism Reaction ID
diisopropyl fluorophosphate + H2O = diisopropyl phosphate + fluoride the catalytic mechanism of DFPase is investigated using the hybrid density functional theory method B3LYP with a large quantum chemical model of the active site abstracted from the X-ray crystal structure. For the first step, two different pathways are considered: (1) residue Asp229 as a nucleophile inline attacks on the phosphorus center and (2) an activated water molecule as the nucleophile attacks on the phosphorus center. Both the Asp229 and the activated water molecule are capable of proceeding nucleophilic attack on the substrate in the presence of Ca2+ ion with the associated barriers 14.8 and 6.0 kcal/mol, respectively. The latter is much easier to perform the nucleophile attack. From the phosphoenzyme intermediate with the hexa-coordinated Ca2+, the uncoordinated Glu21 functions as a general base activated an additional water molecule to attack the carbon center of Asp229 and make the phosphate release. Residues Asn120 and Asn175 promote the elimination of the fluoride via donating strong hydrogen bonds. Residue Asp229 plays a dual role during the hydrolysis reaction process, either as a nucleophile or as a general base to activate the water nucleophile. The role of the calcium ion is providing a necessary conformation of the active site, facilitating the nucleophile formation and substrate orientation Loligo vulgaris
a

Source Tissue

Source Tissue Comment Organism Textmining
head ganglion
-
 Loligo vulgaris
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
diisopropyl fluorophosphate + H2O
-
 Loligo vulgaris diisopropyl phosphate + fluoride
-
 ?
additional information DFPase from Loligo vulgaris effectively catalyzes the hydrolysis of the bond between phosphorus and the fluoride (or cyanide) leaving group Loligo vulgaris ?
-
 ?

Subunits

Subunits Comment Organism
? x * 35000, SDS-PAGE Loligo vulgaris

Synonyms

Synonyms Comment Organism
DFPase
-
 Loligo vulgaris

General Information

General Information Comment Organism
additional information residue Asp229 plays a role in the coordination variation of calcium during the reaction. Quantum mechanical/molecular mechanical umbrella sampling simulations displays that the hydrolysis of diisopropyl fluorophosphate (DFP) and (S)-sarin processes by DFPase presents two different reaction pathways involving nucleophilic attack by Asp229 or an activated water on phosphorus. Modeling of active site and reaction mechanism with nucleophile Asp229 and coordinating Ca2+, detailed overview. Optimized geometries for the intermediates, transition state, and product for the hydrolysis step of DFPase Loligo vulgaris
physiological function the enzyme efficiently catalyze the hydrolysis of the substrate diisopropyl fluorophosphate and a wide range of organophosphorus nerve agents, including soman, sarin, and tabun Loligo vulgaris