Table 1. Conserved ETaG Mutant Residuesa.
| predominant
residue (abundance) |
||||
|---|---|---|---|---|
| positionb | Pho85 | ETaG | distance to ATP-γ-S/Å | human CDK2c |
| 66 | Val (92%) | Leu (93%) | 4.9 | 64 Val |
| 69 | His (66%) | Tyr (53%) | 8.8 | 67 Leu |
| 79 | Met (57%) | Ile (56%) | 12.4 | 77 Tyr |
| 82 | Phe (87%) | Ser (88%) | 4.4 | 80 Phe |
| 123 | Phe (54%) | Tyr (52%) | 17.3 | 117 Phe |
| 129 | Val (58%) | Ile (55%) | 14.6 | 123 Val |
| 150 | Gly (58%) | Ala (58%) | 7.9 | 144 Ala |
| 176 | Ala (64%) | Pro (57%) | 17.8 | 170 Ala |
a
Residue conservation analysis between housekeeping Pho85 and ETaG proteins identified 8 candidate resistance mutations that differ between housekeeping (Pho85) and ETaG sets, and are more than 50% conserved in each set. Three of these residues (bold) are within 8 Å of the active site (PDB ID 2PMI)25 and are proposed here to be determinants of GEM resistance in the ETaG.
b
Positions are in reference to yeast Pho85 (Uniprot ID P17157).
c
Human CDK2 (Uniprot ID P24941).