SerHisGlu

SerHisGlu is a proposed catalytic motif consisting of serine (Ser), histidine (His), and glutamate (Glu) residues posited to form a triad in a subset of serine hydrolases and designed enzymes. It is described as an alternative to the classic Ser-His-Asp triad, with glutamate serving as the acidic partner to histidine. The concept arises from structural and mechanistic studies that explore how different acid-base partners can support nucleophilic activation in enzyme active sites.

In the SerHisGlu arrangement, serine acts as the nucleophile, histidine serves as a general base to activate serine, and glutamate stabilizes the imidazole of histidine through a hydrogen-bond network, helping to tune the pKa and facilitate proton transfer during catalysis. The exact geometry and longer-range interactions required for efficient turnover depend on the surrounding second-shell residues and local topology.

Evidence for SerHisGlu comes mainly from computational modeling, design studies, and limited experimental work on engineered enzymes. Natural proteins explicitly employing a canonical Ser-His-Glu triad are not broadly cataloged, and the motif remains a topic of investigation rather than a widely accepted standard. Researchers use SerHisGlu as a conceptual framework to test alternative catalytic strategies and to diversify the repertoire of serine hydrolases.

If validated, SerHisGlu could broaden understanding of catalytic versatility in proteomes and inform enzyme design aimed at tailoring substrate specificity and reaction conditions. See also: catalytic triad, serine hydrolases, Ser-His-Asp.