@misc{10481/84039,
year = {2023},
month = {5},
url = {https://hdl.handle.net/10481/84039},
abstract = {Enzymes catalyze the chemical reactions of life. For nearly half of known enzymes, catalysis requires the binding of
small molecules known as cofactors. Polypeptide-cofactor complexes likely formed at a primordial stage and became
starting points for the evolution of many efficient enzymes. Yet, evolution has no foresight so the driver for the primordial
complex formation is unknown. Here, we use a resurrected ancestral TIM-barrel protein to identify one potential
driver. Heme binding at a flexible region of the ancestral structure yields a peroxidation catalyst with
enhanced efficiency when compared to free heme. This enhancement, however, does not arise from proteinmediated
promotion of catalysis. Rather, it reflects the protection of bound heme from common degradation
processes and a resulting longer lifetime and higher effective concentration for the catalyst. Protection of catalytic
cofactors by polypeptides emerges as a general mechanism to enhance catalysis and may have plausibly benefited
primordial polypeptide-cofactor associations.},
organization = {Human Frontier Science Program grant RGP0041/2017},
organization = {National Science Foundation grant 2032315},
organization = {Department of Defense grant MURI W911NF-16-1-0372},
organization = {National Institutes of Health grant R01AR069137},
organization = {Spanish Ministry of Science and Innovation/ FEDER Funds grant PID2021-124534OB-100},
organization = {Grant PID2020-116261GB-I00},
publisher = {Oxford academy},
title = {Protection of Catalytic Cofactors by Polypeptides as a Driver for the Emergence of Primordial Enzymes},
doi = {10.1093/molbev/msad126},
author = {Gutiérrez Rus, Luis Ignacio and Gámiz Arco, María Gloria and Gavira Gallardo, José Antonio and Risso, Valeria Alejandra and Sánchez Ruiz, José Manuel},
}