ArticleProceedings of the National Academy of Sciences of the United States of America2020
Short and simple sequences favored the emergence of N-helix phospho-ligand binding sites in the first enzymes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Compositionally Biased Regions Within Structured Protein Domains.Biomolecules · 2026Article
- The history of enzyme evolution embedded in metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Contrastive learning unites sequence and structure in a global representation of protein space.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Borderlands of Foldability: Lessons from Simplified Proteins.Trends in chemistry · 2026Article
- Physics Determines and Evolution Shapes Basic Units of Protein Function and Allosteric Regulation.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Coenzyme-protein interactions since early life.eLife · 2025Article
- ATP allosterically regulates an acyl-CoA oxidase.Nature communications · 2025Article
- On the emergence of metabolism: the evolution of proteins that powered life.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Distribution of Polyphosphate Kinase 2 Genes in Bacteria Underscores a Dynamic Evolutionary History.Proteins · 2025Article
- Role of Electron Spin, Chirality, and Charge Dynamics in Promoting the Persistence of Nascent Nucleic Acid-Peptide Complexes.The journal of physical chemistry. B · 2025Article
- Redefining the Limits of Functional Continuity in the Early Evolution of P-Loop NTPases.Molecular biology and evolution · 2025Article
- multistrap: boosting phylogenetic analyses with structural information.Nature communications · 2025Article
- Peptides En Route from Prebiotic to Biotic Catalysis.Accounts of chemical research · 2024Article
- Immunoanalytical Detection of Conserved Peptides: Refining the Universe of Biomarker Targets in Planetary Exploration.Analytical chemistry · 2024Article
- Back in time to the Gly-rich prototype of the phosphate binding elementary function.Current research in structural biology · 2024Review
- On the Origins of Enzymes: Phosphate-Binding Polypeptides Mediate Phosphoryl Transfer to Synthesize Adenosine Triphosphate.Journal of the American Chemical Society · 2023Article
- An evolutionary history of the CoA-binding protein Nat/Ivy.Protein science : a publication of the Protein Society · 2022Review
- Uniform binding and negative catalysis at the origin of enzymes.Protein science : a publication of the Protein Society · 2022Article
- Mechanisms of protein evolution.Protein science : a publication of the Protein Society · 2022Review
- Bridging Themes: Short Protein Segments Found in Different Architectures.Molecular biology and evolution · 2021Article
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4 authors.
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Abstract
The ubiquity of phospho-ligands suggests that phosphate binding emerged at the earliest stage of protein evolution. To evaluate this hypothesis and unravel its details, we identified all phosphate-binding protein lineages in the Evolutionary Classification of Protein Domains database. We found at least 250 independent evolutionary lineages that bind small molecule cofactors and metabolites with phosphate moieties. For many lineages, phosphate binding emerged later as a niche functionality, but for the oldest protein lineages, phosphate binding was the founding function. Across some 4 billion y of protein evolution, side-chain binding, in which the phosphate moiety does not interact with the backbone at all, emerged most frequently. However, in the oldest lineages, and most characteristically in αβα sandwich enzyme domains, N-helix binding sites dominate, where the phosphate moiety sits atop the N terminus of an α-helix. This discrepancy is explained by the observation that N-helix binding is uniquely realized by short, contiguous sequences with reduced amino acid diversity, foremost Gly, Ser, and Thr. The latter two amino acids preferentially interact with both the backbone amide and the side-chain hydroxyl (bidentate interaction) to promote binding by short sequences. We conclude that the first αβα sandwich domains emerged from shorter and simpler polypeptides that bound phospho-ligands via N-helix sites.
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