Table II.
Biochemical and Biological Impacts of Dominant-Negative Heterozygous Mutations (H391Y, K422R)(37,38)
| S. no. | Features | Wild PKM2 | H391Y | K422R |
|---|---|---|---|---|
| 1 | Enzymatic activity | 100% | 80% | 25% |
| 2 | PEP affinity | Normal | Increased by sixfold | Reduced by threefold |
| 3 | Catalytic efficiency | Normal | Increased | Reduced |
| 4 | Oligomeric state | Homotetramer | Homotetramer | Homotetramer |
| 5 | Cooperativity | Allosteric | Completely lost | Increased |
| 6 | Activation by FBP | Yes | No | Yes |
| 7 | Optimum pH | 7.4 | 7.0 | 7.0 |
| 8 | Thermostability | No | Yes | No |
| 9 | α Helical content | Rich | Increased | Increased |
| 10 | Structural rigidity | Absent | Present | Absent |
| When coexpressed with PK-WT in in vitro transfection assays | ||||
| 11 | Cross-monomer interaction | Yes | Yes | Yes |
| 12 | Oligomeric state | Normal | Disturbed | Disturbed |
| 13 | Heterooligomerization | Yes | Yes | Yes |
| 14 | Heterodimerization | No | Yes | Yes |
| 15 | Enzymatic activity | Unaffected | Reduced | Reduced |
| 16 | PEP affinity | Unaffected | Reduced | Reduced |
| 17 | E. coli doubling time | Slightly reduced | Reduced | Reduced |
| 18 | Rate of cell division | Slightly increased | Promoted | Promoted |
| 19 | Polyploidy | Unaffected | Promoted | Promoted |