Motivation: Antimicrobial resistance databases are central to genomic surveillance, but resistance determinants remain distributed across resources with different scopes, structures, and annotations. Results: We developed PanRes, a curated resistance database of 11 717 genes integrating acquired and latent determinants of antibiotic, biocide, and metal resistance within a unified ontology. We predicted representative protein structures and clustered them by structural similarity, grouping proteins into 505 high-confidence structurally conserved clusters coherent despite sequence divergence. Their structure-guided alignments were used to build Hidden Markov Models (HMMs) for remote homology search. In seven wastewater metagenomes from five European cities, PanRes 3D-based HMMs expanded detection beyond what was possible with BLAST, with 35.3% of retained hits identified only by the HMMs and generally showing greater divergence from known proteins. For beta-lactamases, several proteins retained beta-lactamase-like folds and catalytic geometry despite weak sequence similarity. Availability and implementation: PanRes is available through an interactive web platform (https://panres.rambio.dk/), a structure-informed resource for exploring the whole resistome. The database, HMM profiles, and ontology are available at Zenodo (10.5281/zenodo.22876216).

Antimicrobial resistance databases are central to genomic surveillance, but resistance determinants remain distributed across resources with different scopes, structures, and annotations. We developed PanRes, a curated resistance database of 11,717 genes integrating acquired and latent determinants of antibiotic, biocide, and metal resistance within a unified ontology. We predicted representative protein structures and clustered them by structural similarity, grouping proteins into 598 structurally conserved clusters coherent despite sequence divergence. Their structure-guided alignments were used to build Hidden Markov Models (HMMs) for remote homology search. In wastewater metagenomes from seven European cities, PanRes 3D-based HMMs expanded detection beyond high-confidence BLAST, with 35.2% of retained hits identified only by the HMMs and generally showing greater divergence from known proteins. For beta-lactamases, several proteins retained beta-lactamase-like folds and catalytic geometry despite weak sequence similarity. PanRes is available through an interactive web platform (https://panres.rambio.dk/), a structure-informed resource for exploring the whole resistome.