Table II.
Thermodynamic Comparison of AAC-IIIb and AAC-IIa
| KD (μM) | ΔHint (kcal/mol) | –TΔS (kcal/mol) | ΔG (kcal/mol) | Δn | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Complex | IIIb | IIa | IIIb | IIa | IIIb | IIa | IIIb | IIa | IIIb | IIa |
| Sisomicin (B)a | 10.3 | 1.5 | −5.5 | −49 | −1.3 | 41 | −6.8 | −8.0 | 0.34 | 2.8 |
| Sisomicin (T) | 1.7 | 0.1 | −14.9 | −9.7 | 7.2 | −0.30 | −7.7 | −10.0 | 0.66 | −0.34 |
| Tobramycin (B) | 33.0 | 34 | −8.4 | −16 | 2.3 | 9.9 | −6.2 | −6.1 | 0.60 | 1.1 |
| Tobramycin (T) | 2.9 | 1.7 | −22.2 | −7.6 | 14.6 | 0.04 | −7.6 | −7.6 | 1.0 | −0.10 |
| Kanamycin B (B) | 30.0 | 130 | −8.1 | −12 | 1.9 | 6.7 | −6.2 | −5.3 | 0.60 | 0.90 |
| Kanamycin B (T) | 3.9 | 7.8 | −26.0 | −8.6 | 18.6 | 1.6 | −7.4 | −7.0 | 1.5 | 0.30 |
| Kanamycin A (B) | 79.8 | 110 | −1.2 | −1.6 | −4.4 | −4.0 | −5.6 | −5.6 | −0.07 | −0.47 |
| Kanamycin A (T) | 16.0 | 2.2 | −12.8 | −9.9 | 6.2 | 2.1 | −6.6 | −7.8 | 1.3 | 0.02 |
| CoASHb | 1.9 | 9.7 | 0.4 | −23 | −8.2 | 17 | −7.8 | −6.0 | ND | 1.4 |
| CoASH (Tob) | 2.5 | 1.6 | −16.7 | −12 | 9.0 | 4.1 | −7.7 | −7.9 | 0.60 | 0.14 |
| CoASH (KanB) | 2.0 | 1.6 | −19.8 | −18 | 11.9 | 9.7 | −7.8 | −8.3 | 0.80 | 0.69 |
| CoASH (KanA) | 6.6 | 1.1 | −20.8 | −13 | 13.6 | 5.0 | −7.2 | −8.0 | 1.4 | 0.23 |
| CoASH (Siso) | 2.3 | 0.8 | −10.8 | −9 | 3.1 | 0.6 | −7.7 | −8.4 | 0.5 | −0.04 |
“(B)” indicates data for the formation of the respective binary complex (i.e., AAC-tobramycin) while “(T)” stands for the ternary complex formed by antibiotic titration into the AAC-CoASH complex. The bottom four complexes are CoASH titration into an AAC-antibiotic complex with the antibiotic given in parenthesis. Results are averages from two to three trials with standard errors of the mean of ≤10%. Data for AAC-IIIb is presented with permission from Ref.8.
a
Binding stoichiometry was ∼0.6.
b
Intrinsic enthalpy could not be determined for CoASH binding to AAC-IIIb due to the weak heat of association. The reported value was determined in Tris buffer.