A de novo protein binder targeting the CD38 catalytic cleft (hotspot residues C119, K121, W125, F143, E146, D155, L157, Q226 from PDB 2I65, 1.9 Å resolution) is hypothesized to competitively inhibit CD38 NADase/cyclase activity and elevate tissue NAD+ levels in aged tissues, counteracting the NAD+ decline hallmark of aging.
Details
- local_id
- claim-cd38-nadsase-inhibition-hypothesis
- confidence
- moderate
- created_by
- persona-kris-ganjam
Raw fields (3)
- tags
[ "CD38", "NAD+", "senescence", "anti-aging", "BindCraft", "catalytic-inhibition" ]
- links
{ "source_papers": [], "source_datasets": [ "PDB:2I65", "UniProt:P28907" ], "supporting_figures": [] }- analysis
CD38 (UniProt P28907) is the dominant NAD+ consumer in aged tissues. Catalytic cleft hotspot residues C119, K121, D155, D156, L157, D179, C201 were identified from PDB 2I65 (apo, 1.9 Å) and PDB 4XJS (inhibitor-bound, 2.8 Å, quinoline carboxamide). Centroid coordinates locked for BindCraft conditioning: C119(-10.921, 6.311, -9.356), K121(-14.362, 5.x, x.x). Identification strategy: in_silico_KO.