@misc{10481/103884,
year = {2025},
month = {3},
url = {https://hdl.handle.net/10481/103884},
abstract = {At the heart of many nucleoside triphosphatases is a conserved phosphate-binding sequence motif. A current model of early enzyme evolution
proposes that this six to eight residue motif could have sparked the emergence of the very first nucleoside triphosphatases—a striking example of
evolutionary continuity from simple beginnings, if true. To test this provocative model, seven disembodied Walker A-derived peptides were
extensively computationally characterized. Although dynamic flickers of nest-like conformations were observed, significant structural similarity
between the situated peptide and its disembodied counterpart was not detected. Simulations suggest that phosphate binding is nonspecific,
with a preference for GTP over orthophosphate. Control peptides with the same amino acid composition but different sequences and situated
conformations behaved similarly to the Walker A peptides, revealing no indication that the Walker A sequence is privileged as a disembodied
peptide. We conclude that the evolutionary history of the P-loop NTPase family is unlikely to have started with a disembodied Walker A
peptide in an aqueous environment. The limits of evolutionary continuity for this protein family must be reconsidered. Finally, we argue that
motifs such as the Walker A motif may represent incomplete or fragmentary molecular fossils—the true nature of which has been eroded by time.},
organization = {Knut and Alice Wallenberg Foundation (grant numbers 2018.0140 and 2019.0431)},
organization = {Okinawa Institute of Science and Technology Graduate University (OIST) with subsidy funding from the Cabinet Office, Government of Japan},
organization = {National Academic Infrastructure for Supercomputing in Sweden (NAISS), partially funded by the Swedish Research Council through grant agreement no. 2022-06725},
publisher = {Oxford University Press},
keywords = {Walker A motif},
keywords = {P-loop NTPase},
keywords = {Phosphate-binding loop},
title = {Redefining the Limits of Functional Continuity in the Early Evolution of P-Loop NTPases},
doi = {10.1093/molbev/msaf055},
author = {Demkiv, Andrey O. and Toledo-Patiño, Saacnicteh and Medina Carmona, Encarnación and Berg, Andrej and Pinto, Gaspar P. and Parracino, Antonietta and Sánchez Ruiz, José Manuel and Hengge, Alvan C. and Laurino, Paola and Longo, Liam M. and Kamerlin, Shina CL},
}