Application | Comment | Organism |
---|---|---|
medicine | fosfomycin is a clinically useful antibiotic for the treatment of limb-threatening diabetic foot infections and lower urinary tract infections. It is effective against ciprofloxacin-resistant Escherichia coli, as well as methicillin-resistant and vancomycin-resistant strains of Staphylococcus aureus. The antimicrobial activity of fosfomycin is due to the inactivation of UDP-GlcNAc-3-O-enolpyruvyltransferase, which catalyzes the first committed step in the biosynthesis of peptidoglycan, the main component of the bacterial cell wall | Pseudomonas syringae |
Cloned (Comment) | Organism |
---|---|
expression in Escherichia coli | Pseudomonas syringae |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
EDTA | 5 mM, abolishes activity | Pseudomonas syringae |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Iron | mononuclear non-heme iron-containing enzyme. Contains about one iron per monomer. Substrate and NO can bind to the ferrous center of the reduced HppE enzyme to form a stable complex | Pseudomonas syringae |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
21000 | - |
3 * 21000, SDS-PAGE | Pseudomonas syringae |
21315 | - |
3 * 21315, calculated from sequence | Pseudomonas syringae |
73000 | - |
gel filtration | Pseudomonas syringae |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
(S)-2-hydroxypropylphosphonic acid + 2 NADH + O2 | Pseudomonas syringae | - |
cis-(1R,2S)-epoxypropylphosphonic acid + 2 H2O + 2 NAD+ | i.e. fosfomycin | ? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Pseudomonas syringae | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
side-chain modification | posttranslationally modified by the hydroxylation of Tyr95 | Pseudomonas syringae |
Purification (Comment) | Organism |
---|---|
- |
Pseudomonas syringae |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
(S)-2-hydroxypropylphosphonate + H2O2 = (1R,2S)-1,2-epoxypropylphosphonate + 2 H2O | electron transfer is presumed to be the predominant rate-limiting step. Proposed mechanism: the reaction likely begins with hydrogen atom abstraction from the C-1 position by an activated oxygen species. The C-1 centered radical intermediate can then cyclize to form fosfomycin and the reduced iron center | Pseudomonas syringae |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
(S)-2-hydroxypropylphosphonic acid + 2 NADH + O2 | - |
Pseudomonas syringae | cis-(1R,2S)-epoxypropylphosphonic acid + 2 H2O + 2 NAD+ | i.e. fosfomycin | ? | |
(S)-2-hydroxypropylphosphonic acid + 2 NADH + O2 | if either iron, FMN, or NADH is omitted from the reaction mixture, no product formation is detected | Pseudomonas syringae | cis-(1R,2S)-epoxypropylphosphonic acid + 2 H2O + 2 NAD+ | i.e. fosfomycin | ? | |
additional information | the enzyme also forms 2-oxopropylphosphonic acid from (R)-2-hydroxypropylphosphonic acid, the rate of this reaction is 1.9times faster than the reaction with (S)-2-hydroxypropylphosphonic acid | Pseudomonas syringae | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
trimer | 3 * 21000, SDS-PAGE | Pseudomonas syringae |
trimer | 3 * 21315, calculated from sequence | Pseudomonas syringae |
Synonyms | Comment | Organism |
---|---|---|
HPP epoxidase | - |
Pseudomonas syringae |
HppE | - |
Pseudomonas syringae |
Ps-HppE | - |
Pseudomonas syringae |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0028 | - |
(S)-2-hydroxypropylphosphonic acid | pH 7.5 | Pseudomonas syringae |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Pseudomonas syringae |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
FMN | if either iron, FMN, or NADH is omitted from the reaction mixture, no product formation is detected. Due to the fact that the reduction of iron requires single electron transfer and NADH is an obligate two-electron donor, FMN is required to mediate the transfer of reducing equivalents from NADH to the active site iron | Pseudomonas syringae | |
NADH | NADH is essential for catalysis | Pseudomonas syringae |