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Literature summary for 2.7.1.95 extracted from
- Kinetic characterization and molecular docking of novel allosteric inhibitors of aminoglycoside phosphotransferases (2017), Biochim. Biophys. Acta, 1861, 3464-3473 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene aphA, recombinant expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3) | Enterococcus faecalis |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| R211A | site-directed mutagenesis | Enterococcus faecalis |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | identification os specific inhibitors of APHs that can restore bacterial susceptibility to aminoglycosides, screening of the Zinc database for search for allosteric inhibitors that bind to small cavities of the protein and block the enzyme function by perturbing its dynamics, docking study usig the crystal structure of the enzyme (PDB ID 1L8T) with removed aminoglycoside substrate, overview. The two interactions with side chain of Arg211 and backbones of Leu209 and Gly210 are shown to play an essential role in the inhibition of APH. No inhibition by ZINC20785546, ZINC20737652, ZINC40455179, ZINC6751595, ZINC14746000, ZINC36589946, and ZINC22357542 | Enterococcus faecalis | |
| ZINC05277506 | - |
Enterococcus faecalis | |
| ZINC08981682 | 7% inhibition at 0.5 mM | Enterococcus faecalis | |
| ZINC1143187 | 12% inhibition at 0.5 mM | Enterococcus faecalis |  |
| ZINC12636347 | 37% inhibition at 0.5 mM | Enterococcus faecalis | |
| ZINC13001089 | - |
Enterococcus faecalis | |
| ZINC13001091 | 7% inhibition at 0.5 mM | Enterococcus faecalis | |
| ZINC13236811 | 43% inhibition at 0.5 mM, 43% inhibition of APH(3')-IIIa, ZINC13236811 acts again as a non-competitive inhibitor towards ATP and kanamycin A | Enterococcus faecalis | |
| ZINC13572054 | 37% inhibition at 0.5 mM | Enterococcus faecalis | |
| ZINC1792615 | 8% inhibition at 0.5 mM | Enterococcus faecalis | |
| ZINC22406103 | 20% inhibition at 0.5 mM | Enterococcus faecalis | |
| ZINC36046879 | - |
Enterococcus faecalis | |
| ZINC52627502 | - |
Enterococcus faecalis | |
| ZINC8790387 | 79% inhibition at 0.5 mM, competitive inhibitor of APH(3')-IIIa towards ATP, and non-competitive inhibitor towards kanamycin A. The inhibitor may bind to a different location, presumably closer to the nucleotide binding pocket without interfering with the aminoglycoside site | Enterococcus faecalis | |
| ZINC8981627 | 3% inhibition at 0.5 mM | Enterococcus faecalis | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | steady-state kinetics | Enterococcus faecalis |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Enterococcus faecalis | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + kanamycin | Enterococcus faecalis | - |
ADP + kanamycin 3'-phosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Enterococcus faecalis | P0A3Y5 | - |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + kanamycin | - |
Enterococcus faecalis | ADP + kanamycin 3'-phosphate | - |
? | |
| additional information | enzyme assay with coupling the release of ADP to a pyruvate kinase/lactate dehydrogenase reaction | Enterococcus faecalis | ? | - |
- |
|
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| aminoglycoside 3'-phosphotransferase | UniProt | Enterococcus faecalis |
| aminoglycoside phosphotransferase | - |
Enterococcus faecalis |
| APH | - |
Enterococcus faecalis |
| APH(3')-IIIa | - |
Enterococcus faecalis |
| AphA | - |
Enterococcus faecalis |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 25 | - |
assay at | Enterococcus faecalis |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.5 | - |
assay at | Enterococcus faecalis |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Enterococcus faecalis | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.009 | - |
ZINC8790387 | pH 7.5, 25°C, recombinant enzyme, versus ATP | Enterococcus faecalis | |
| 0.055 | - |
ZINC8790387 | pH 7.5, 25°C, recombinant enzyme, versus kanamycin | Enterococcus faecalis | |
| 0.075 | - |
ZINC13236811 | pH 7.5, 25°C, recombinant enzyme, versus ATP | Enterococcus faecalis | |
| 0.076 | - |
ZINC13236811 | pH 7.5, 25°C, recombinant enzyme, versus kanamycin | Enterococcus faecalis | |
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