K800E
Category 3/4 — Most DruggableConflictingLumenal · predictedσ-1 candidateEditorialLysine → Glutamate at position 800 in lumenal domain. ClinVar Conflicting. AlphaMissense 0.778, ΔΔG -0.40. pLDDT 72 borderline. Same K800-D801 salt-bridge pair as D801G.
Interactive 3D Structure
Bond changes · DynaMut2 interaction analysis
| Interaction type | Wild-type partner | Mutant partner | Status |
|---|---|---|---|
| Ionic bond | E794 | — | Lost |
| Hydrogen bond | E794 | — | Lost |
| Hydrogen bond | D797 | D797 | Preserved |
| Polar contact | — | W666 | Gained |
| Polar contact | E794 | — | Lost |
| Polar contact | D797 | D797 | Preserved |
| Polar contact | V798 | V798 | Preserved |
| Hydrophobic | D797 | — | Lost |
Lost / gained / preserved interatomic contacts at the variant residue, from the DynaMut2 (Arpeggio) interaction analysis of the wild-type and energy-minimized mutant structures.
Computational Predictions
Clinical Evidence
Observed in the general population.
Structural Context
Position 800 sits adjacent to D801. Neighbors: ASP801 (2.5 Å — D801G Atlas card!), THR799 (2.5 Å), ASP797 (3.7 Å), VAL798 (4.3 Å).
The wild-type K800-D801 salt bridge (referenced in D801G Atlas card) breaks when K800 becomes E800: now TWO adjacent glutamates (E800, D801) with no positive charge to stabilize. The local electrostatic environment is transformed. ΔΔG 0.40 + AM 0.778 confirm severe consequence.
Druggability Assessment
Mechanism: K800-D801 salt bridge broken by charge-flip at K800. Therapeutic: same K800-D801 microregion as D801G.
Why this matters
Feed this card to Wolfram Intelligence
Download the K800E PDF below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals — guanidinium mimetics, sigma-1 agonist docking, NAC thiol-capping. NAC is already on the bench-testing list.