Table 1.
IC50, inhibition constants (Ki), dissociation constants (Kd), stoichiometry (n), and thermodynamics parameters for 3-((2-naphthylmethyl)sulfanyl)-4H-1,2,4-triazole (A-310840) and ((2RS,3R)-3-amino-2-hydroxy-5-ethylthio)pentanoyl-((S)-(−)-(1-naphthyl)ethyl) amide (A-311263) binding to Co(II)- and Mn(II)-loaded type-II methionine aminopeptidase (MetAP) from Pyrococcus furiosus (PfMetAP-II) and type-I MetAP from Escherichia coli (EcMetAP-I)
| Wild-type enzymes | n | IC50 (μM) | Ki (μM) | Kd (μM) | ΔH (kJ/mol) | TΔS (J/mol) | ΔG (kJ/mol) |
|---|---|---|---|---|---|---|---|
| A-310840 binding to wild-type enzymes | |||||||
| [CoCo(PfMetAP-II)] | 1 | 15 | 3 | 2.0 ± 0.1 | −5.5 ± 2 | 27 × 103 | −32.5 |
| [MnMn(PfMetAP-II)] | 1 | 1,000 | 440 | 666 ± 10 | −0.3 ± 0.1 | 17 × 103 | −18.1 |
| [CoCo(EcMetAP-I)] | 1 | 44 | 8 | 10 ± 0.1 | 8.36 ± 0.3 | 20 × 103 | −28.5 |
| [MnMn(EcMetAP-I)] | 1 | 1,000 | 750 | 714 ± 10 | −24.6 ± 3 | −7 × 103 | −17.9 |
| A-311263 binding to wild-type enzymes | |||||||
| [CoCo(PfMetAP-II)] | 1 | 20 | 2 | 0.45 ± 0.11 | −14.9 ± 2 | 21 × 103 | −36.2 |
| [MnMn(PfMetAP-II)] | 1 | 27 | 20 | 26 ± 5 | −62.7 ± 5 | −36 × 103 | −26.1 |
| [CoCo(EcMetAP-I)] | 1 | 32 | 3 | 2.4 ± 0.1 | 1.57 ± 0.3 | 33 × 103 | −32 |
| [MnMn(EcMetAP-I)] | 1 | 34 | 20 | 50 ± 5 | −19 ± 4 | 6 × 103 | −24.5 |