Table 1.
Retro- and prospectively predicted reactive lysines and cysteines in the human protein kinasesa
| Kinase Name | Kinase Group | PDB ID | Catalytic Lys | Calc pKa | Other Reactive Lys | Calc pKa | All Reactive Cys | Calc pKa | Inhibitor Type |
|---|---|---|---|---|---|---|---|---|---|
| ABL1 | TK | 2G2F | C305 (β4–β5) | 8.0 | II | ||||
| EGFR | TK | 5U8L | K745 | 7.3 | C781 (β4–β5) | 8.1 | II | ||
| EGFRmt | TK | 5UG8 | K745 | 7.1 | C781 (β4–β5) | 8.1 | II | ||
| MET | TK | 4MXC | K1110 | 7.7 | II | ||||
| c-SRC | TK | 5K9I | K295 | 8.1 | C277 (P-loop) | 6.8 | II | ||
| LIMK2 | TKL | 4TPT | C365 (β3–αC) | 5.8 | III | ||||
| RIPK1 | TKL | 4ITJ | K45 | 6.7 | C53 (β3–αC) | 8.3 | III | ||
| LOK | STE | 4USD | C206 (A-loop) | 7.6 | II | ||||
| PAK1 | STE | 4ZLO | C411 (DFG+2, built) | 5.0 | II | ||||
| PDK1 | AGC | 3NAX | K111 | 7.0 | C260 (A-loop to αF) | 6.0 | II | ||
| CDK6 | CMGC | 1G3N | K43 | 6.1 | K147 (HRD+2) | 6.0 | C15 (β1) | 7.9 | II |
| NEK2 | Other | 2XNM | K37 | 7.8 | II | ||||
| Aurora | Other | 4JAI | K162 | 7.9 | C290 (A-loop, built) | 5.4 | II | ||
| IRE1α | Other | 4YZ9 | C747 (A-loop, built) | 7.9 | II | ||||
| C715 (DFG+2) | 5.8 | ||||||||
| PEK | Other | 4X7N | K622 | 7.6 | K939 (HRD+2) | 7.3 | C1049 (αH) | 5.2 | II |
a
Only kinases with at least one reactive lysine or cysteine (see main text for definitions) are listed. The complete list is given in Table S1. Locations for non-catalytic residues are indicated in parentheses. EGFRmt refers to the mutant L858R/T790M. c-SRC is included as a part of the validation set. The pKa calculations for cysteines used the second halves of the simulations. Cys290 in Aurora and Cys747 in IRE1α were missing in the PDB les and the positions were built using SWISS-MODEL.39 For CDK6 and PEK, Asp in the commonly-known HRD motif is replaced with Asn.