Table 1.
Carbon Acid (Substrate C-H) pKa values.
| Enzyme (substrate) | Water pKa (experimental)a | Active site pKa (experimental)b | Active site pKa (QM/MM) | ΔpKac |
|---|---|---|---|---|
| COFACTOR INDEPENDENT ENZYMES | ||||
| Ketosteroid isomerase (Δ-3-keto steroid) | 13 | 5.6 | 5.6 | 7.4 |
| Triosephosphate isomerase (GAP) | 17 | 9–12 | 11 | 5–8 |
| Triosephosphate isomerase (DHAP) | 18 | 10–14 | 14–20 | 4–8 |
| Proline racemase (Proline) | 29 | 16 | 16 | 13 |
| Mandelate Racemase (Mandelate) | 30 | 9–15 | 17 | 15–21 |
| Fumarase (Malate) | 30 | 9–13 | – | 17–21 |
| PYRIDOXAL PHOSPHATE DEPENDENT ENZYMES | ||||
| Tryptophan synthase (Tryptophan) | 29 | 8 | – | 21 |
| Tryptophan indole-lyase (Tryptophan) | 29 | 6 | – | 23 |
| Tyrosine phenol-lyase (Phenylalanine) | 29 | 6 | – | 23 |
| Alanine Racemase (Alanine) | 29 | 11 | 12 | 18 |
| Aspartate aminotransferase (Aspartate) | 29 | ~7 | – | ~22 |
| Dialkylglycine decarboxylase (Alanine) | 29 | 8 | – | 21 |
a
The references for C-H pKa values for substrates are given in Supplementary Material.
b
Experimental active site C-H pKa ranges are determined from the lower limit for the carbanion reprotonation rate constant obtained from the FEP and an assumed upper limit of 1012 s-1. Values that are not well-defined are highlighted in italics.
C
The difference in C-H pKa between the substrate in water and in the enzyme active site.