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bioRxiv · 10.64898/2026.10.18.759936

N-Zinclopedia: A database of predicted transition metal-binding sites and metalloenzymes

Mechtinger, G.·Axel, G.·Marcellino, L.·M. Bowman, A.·Slusky, J.·Ben-Tal, N.
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Abstract

Metal ions are among the most common enzymatic cofactors, yet metal utilization remains poorly mapped. Here, we present N-Zinclopedia, an atlas of predicted transition metal-binding sites and candidate metalloenzymes across protein fold space. N-Zinclopedia catalogs protein sites compatible with transition metal coordination, identified using ZincSight screening of protein structure model databases. We focused on previously uncharacterized domains and proteins, screening for transition metal-binding sites within over a million of these, spanning both poorly annotated and canonical folds. We also classified the predicted sites, using MAHOMES-II, as candidate catalytic or non-catalytic metal-binding sites. Experimental characterization of a previously unknown zinc binding site confirms that ZincSight can determine previously un-annotated zinc binding. N-Zinclopedia significantly expands the known landscape of metal utilization, providing numerous predictions that await experimental examination. N-Zinclopedia is available at: https://bentallab.github.io/nzinclopedia.

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Mechtinger, G., Axel, G., Marcellino, L., M. Bowman, A., Slusky, J., Ben-Tal, N.. 2026-10-19. N-Zinclopedia: A database of predicted transition metal-binding sites and metalloenzymes. https://doi.org/10.64898/2026.10.18.759936

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