ArticlePLoS computational biology2019
Functional analysis of Rossmann-like domains reveals convergent evolution of topology and reaction pathways.
Article in PLoS computational biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed.
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- Protein folds and catalytic strategies at the origin of biological CO2 fixation.FEMS microbiology ecology · 2026Article
- ECOD: Classification of domains in AFDB Swiss-Prot structure predictions.PLoS computational biology · 2026Article
- Metagenomic analysis of the fungal community present in unimpacted and oil-impacted soil, South Shetland Islands, maritime Antarctica.World journal of microbiology & biotechnology · 2026Article
- ATP-Driven Allosteric Regulation of 14-3-3: Positive Modulation of ATP Hydrolysis and Negative Regulation of Peptide Binding.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- DrugDomain 2.0: comprehensive database of protein domains-ligands/drugs interactions across the whole Protein Data Bank.bioRxiv : the preprint server for biology · 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
- Leveraging AI to explore structural contexts of post-translational modifications in drug binding.Journal of cheminformatics · 2025Article
- Tubulin Polymerization Promoting Proteins: Functional Diversity With Implications in Neurological Disorders.Journal of neuroscience research · 2025Review
- Structure-Based Mechanism and Specificity of Human Galactosyltransferase β3GalT5.Journal of the American Chemical Society · 2025Article
- Leveraging AI to Explore Structural Contexts of Post-Translational Modifications in Drug Binding.bioRxiv : the preprint server for biology · 2025Article
- DrugDomain 2.0: Comprehensive database of protein domains-ligands/drugs interactions across the whole Protein Data Bank.Computational and structural biotechnology journal · 2025Article
- Protein Fold Usages in Ribosomes: Another Glance to the Past.International journal of molecular sciences · 2024Article
- DrugDomain: The evolutionary context of drugs and small molecules bound to domains.Protein science : a publication of the Protein Society · 2024Article
- Structure classification of the proteins from Salmonella enterica pangenome revealed novel potential pathogenicity islands.Scientific reports · 2024Article
- Reflections on the Origin of Coded Protein Biosynthesis.Biomolecules · 2024Review
- Chalkophomycin Biosynthesis Revealing Unique Enzyme Architecture for a Hybrid Nonribosomal Peptide Synthetase and Polyketide Synthase.Molecules (Basel, Switzerland) · 2024Article
- Architecture, Function, Regulation, and Evolution of α-Glucans Metabolic Enzymes in Prokaryotes.Chemical reviews · 2024Review
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Abstract
Rossmann folds are ancient, frequently diverged domains found in many biological reaction pathways where they have adapted for different functions. Consequently, discernment and classification of their homologous relations and function can be complicated. We define a minimal Rossmann-like structure motif (RLM) that corresponds for the common core of known Rossmann domains and use this motif to identify all RLM domains in the Protein Data Bank (PDB), thus finding they constitute about 20% of all known 3D structures. The Evolutionary Classification of protein structure Domains (ECOD) classifies RLM domains in a number of groups that lack evidence for homology (X-groups), which suggests that they could have evolved independently multiple times. Closely related, homologous RLM enzyme families can diverge to bind different ligands using similar binding sites and to catalyze different reactions. Conversely, non-homologous RLM domains can converge to catalyze the same reactions or to bind the same ligand with alternate binding modes. We discuss a special case of such convergent evolution that is relevant to the polypharmacology paradigm, wherein the same drug (methotrexate) binds to multiple non-homologous RLM drug targets with different topologies. Finally, assigning proteins with RLM domain to the Enzyme Commission classification suggest that RLM enzymes function mainly in metabolism (and comprise 38% of reference metabolic pathways) and are overrepresented in extant pathways that represent ancient biosynthetic routes such as nucleotide metabolism, energy metabolism, and metabolism of amino acids. In fact, RLM enzymes take part in five out of eight enzymatic reactions of the Wood-Ljungdahl metabolic pathway thought to be used by the last universal common ancestor (LUCA). The prevalence of RLM domains in this ancient metabolism might explain their wide distribution among enzymes.
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