The Nϵ‐Rule for Serine, but Not Cysteine Catalytic Triads

Abstract Catalytic triads, composed of a serine or cysteine nucleophile, histidine, and third triad residue (typically Asp/Glu/Asn), are common in enzyme active sites catalyze wide variety chemical reactions. Two types triads can be distinguished: We refer to them as Nδ‐ Nϵ‐configured, depending on whether the histidine imidazole Nδ Nϵ atom is close nucleophile Oγ/Sγ. In this study, we have analyzed configuration. structural more stable Nδ‐configuration predominates. For catalytic configuration depends nucleophile. When it residue, both occur, family. However, when less Nϵ‐configuration almost exclusively found. posit that energetically favored conformation selected for facilitate otherwise difficult proton transfer from residue.