1.13.11.72: 2-hydroxyethylphosphonate dioxygenase
This is an abbreviated version!
For detailed information about 2-hydroxyethylphosphonate dioxygenase, go to the full flat file.
Reaction
Synonyms
HEPD, hydroxyethylphosphonate dioxygenase, PhdP, phpD
ECTree
1.13.11.72 2-hydroxyethylphosphonate dioxygenaseAdvanced search results
results (
results (Substrates Products
Substrates Products on EC 1.13.11.72 - 2-hydroxyethylphosphonate dioxygenase
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
top
SUBSTRATE 
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2R)-hydroxypropylphosphonate + O2
2-oxopropylphosphonate + hydroxymethylphosphonate + acetate
-
substrate partitions between conversion to 2-oxopropylphosphonate and hydroxymethylphosphonate
-
?
(R)-2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
-
product is almost racemic
-
?
(S)-2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
-
product is almost racemic
-
?
1-hydroxy-2,2,2-trifluoroethylphosphonate + O2
trifluoroacetylphosphonate
-
-
-
?
hydroxymethylphosphonate + O2
phosphate + formate
-
-
-
?
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
-
-
-
-
?
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
-
-
-
?
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
-
-
-
ir
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
-
all four electrons required for reduction of O2 are provided by the substrate. Occurence of an intermediate species in which oxygen derived from O2 exchanges with water
-
?
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
catalytic cycle is based on concatenated bifurcations. The first bifurcation is based on the abstraction of hydrogen atoms from the substrate, which leads to a distal or proximal hydroperoxo species Fe-OOH or Fe-(OH)O. The second and the third bifurcations refer to the carbon-carbon bond cleavage reaction achieved through a tridentate intermediate, or employing a proton-shuttle assisted mechanism, in which the residue Glu176 or the FeIV O group serves as a general base. The reaction directions seem to be tunable and show significant environment dependence
-
-
?
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
in the reaction mechanism water molecules serve as an oxygen source in the generation of mononuclear nonheme iron oxo complexes, taking part in the catalytic cycle before the carbon-carbon bond cleavage process. After the dioxygen is bound to the iron center, the dioxygen-bound species Fe-O2 is generated. The abstraction of hydrogen atom from the substrate leads to a distal or proximal hydroperoxo species Fe(III)-OOH. This is the rate-limiting step, which has an energy barrier of 21 and 18 kcal/mol for distal and proximal H-abstraction processes, respectively. The second step is the cleavage of the O-O bond, and the carbon-carbon bond is broken subsequently. In this step, a tridentate binding species and a Fe(IV) sigmaO species are important intermediates to break the carbon-carbon bond. In the third step, the formic acid and the intermediate CH2PO2(OH)- radical are generated. Finally, 2-hydroxyethylphosphonate is converted to hydroxymethylphosphonate, and the formate or formic acid is formed
-
-
?
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
mechanism involves removal of the pro-S hydrogen at C2 and the loss of stereochemical information at C1. Thus, the hydroperoxylation mechanism, previously proposed as the product of a Criegee rearrangement, cannot be operational for conversion of 2-hydroxyethylphosphonate
-
-
?
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
an irreversible step involving O2
-
-
ir
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
the reaction proceeds via a transient iron(IV)-oxo (ferryl) complex, the mechanism involves activation of an O-H bond by the ferryl complex. Maximal accumulation of the intermediate requires both the presence of deuterium in the substrate and, importantly, the use of 2H2O as solvent
-
-
?
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
-
-
-
?
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
the reaction proceeds via a transient iron(IV)-oxo (ferryl) complex, the mechanism involves activation of an O-H bond by the ferryl complex. Maximal accumulation of the intermediate requires both the presence of deuterium in the substrate and, importantly, the use of 2H2O as solvent
-
-
?
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
-
-
-
ir
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
an irreversible step involving O2
-
-
ir
2-hydroxyethylphosphonate + O2
hydroxymethylphosphonate + formate
-
-
-
?
additional information
?
-
proper binding of 2-hydroxyethylphosphonate is important for O2 activation and the enzyme uses a compulsory binding order with 2-hydroxyethylphosphonate binding before O2. In the mechanism, a hydroperoxylation process is followed by a Criegee rearrangement and hydrolysis to form hydroxymethylphosphonate. Thereafter, the P-C bond in the product can be transiently broken, generating phosphite and formaldehyde in the active site of the enzyme. If the formaldehyde is able to rotate along the C=O bond, then phosphite can attack either face of the carbonyl group resulting in a loss of stereochemistry
-
-
?
additional information
?
-
reaction starts with H-abstraction from the C2 position of 2-hydroxyethylphosphonate by a ferric superoxide-type intermediate. The resultant Fe(II)-OOH intermediate may follow either a hydroperoxylation or hydroxylation pathway, the former process being energetically more favorable. In the hydroperoxylation pathway, a ferrous-alkylhydroperoxo intermediate is formed, and then its O-O bond is homolytically cleaved to yield a complex of ferric hydroxide with a gem-diol radical. Subsequent C-C bond cleavage within the gem-diol leads to formation of an R-CH2 radical species and one of the two products, i.e., formic acid. The R-CH2 radical then intramolecularly forms a C-O bond with the ferric hydroxide to provide the other product, hydroxymethylphosphonate. The overall reaction pathway requires ferric superoxide and ferric hydroxide intermediates
-
-
?
additional information
?
-
results provide strong support for a mechanism that proceeds by hydroperoxylation followed by a Criegee rearrangement with a phosphorus-based migrating group and requires that the O-O bond of molecular oxygen is not cleaved prior to substrate activation. No substrate: O-formyl-hydroxymethylphosphonate, (2S)-hydroxypropylphosphonate
-
-
?
additional information
?
-
HEPD oxidizes a relatively unactivated substrate that cannot easily facilitate O2 activation. 2-Hydroxyethylphosphonate does not contain a thiol group that upon binding to the iron can activate it for catalysis, nor does it contain an 2-oxo acid functionality
-
-
?
additional information
?
-
HEPD oxidizes a relatively unactivated substrate that cannot easily facilitate O2 activation. 2-Hydroxyethylphosphonate does not contain a thiol group that upon binding to the iron can activate it for catalysis, nor does it contain an 2-oxo acid functionality
-
-
?
