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

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.