Origin & Evolution of Life

Coenzyme-Protein Interactions Since Early Life

By Keith Cowing
Status Report
November 6, 2023
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Coenzyme-Protein Interactions Since Early Life
Workflow of this study. All available coenzymes in the PDB were identified according to the CoFactor database (Fischer et al., 2010). The PDB entries of structures bound to coenzymes were downloaded programmatically through the PDBe REST API (pdbe.org/api), including the interatomic cofactor-protein interactions, calculated by Arpeggio (Jubb et al, 2017). The coenzyme binding amino acids were mapped to Uniprot databases via SIFTS (Velankar et al., 2013; Dana et al., 2019). PDB entries were grouped by UniProt code; redundancy was removed by clustering the UniProt sequences by 90% sequence identity. — biorxiv

Recent findings in protein evolution and peptide prebiotic plausibility have been setting the stage for reconsidering the role of peptides in the early stages of life’s origin.

Ancient protein families have been found to share common themes and proteins reduced in composition to prebiotically plausible amino acids have been reported capable of structure formation and key functions, such as binding to RNA. While this may suggest peptide relevance in early life, their functional repertoire when composed of a limited number of early residues (missing some of the most sophisticated functional groups of today’s alphabet) has been debated.

Cofactors enrich the functional scope of about half of extant enzymes but whether they could also bind to peptides lacking the evolutionary late amino acids remains speculative. The aim of this study was to resolve the early peptide propensity to bind organic cofactors by analysis of protein-coenzyme interactions across the Protein Data Bank (PDB). We find that the prebiotically plausible amino acids are more abundant in the binding sites of the most ancient coenzymes and that such interactions rely more frequently on the involvement of the protein backbone atoms and metal ion cofactors.

Moreover, we have identified a few select examples in today’s enzymes where coenzyme binding is supported solely by prebiotically available amino acids. These results imply the plausibility of a coenzyme-peptide functional collaboration preceding the establishment of the Central Dogma and full protein alphabet evolution.

Alma Carolina, Sanchez Rocha, Mikhail Makarov, Lukas Pravda, Marian Novotny, Klara Hlouchova



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