5od9

Publication Abstract from PubMed

Primordial sequence signatures in modern proteins imply ancestral origins tracing back to simple peptides. Although short peptides seldom adopt unique folds, metal ions might have templated their assembly into higher-order structures in early evolution and imparted useful chemical reactivity. Recapitulating such a biogenetic scenario, we have combined design and laboratory evolution to transform a zinc-binding peptide into a globular enzyme capable of accelerating ester cleavage with exacting enantiospecificity and high catalytic efficiency (k cat/K M ~ 10(6) M(-1) s(-1)). The simultaneous optimization of structure and function in a naive peptide scaffold not only illustrates a plausible enzyme evolutionary pathway from the distant past to the present but also proffers exciting future opportunities for enzyme design and engineering.

Evolution of a highly active and enantiospecific metalloenzyme from short peptides.,Studer S, Hansen DA, Pianowski ZL, Mittl PRE, Debon A, Guffy SL, Der BS, Kuhlman B, Hilvert D Science. 2018 Dec 14;362(6420):1285-1288. doi: 10.1126/science.aau3744. PMID:30545884^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.