ArticleBiology direct2010
Non-homologous isofunctional enzymes: a systematic analysis of alternative solutions in enzyme evolution.
Article in Biology direct, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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91 citing papers in PubMed.
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- Functional profiling of the sequence stockpile: a protein pair-based assessment of in silico prediction tools.Bioinformatics (Oxford, England) · 2025Article
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- Fine-tuning of conditional Transformers improvesComputational and structural biotechnology journal · 2025Article
- Synthetic lethality and the minimal genome size problem.mSphere · 2024Article
- Enzyme function and evolution through the lens of bioinformatics.The Biochemical journal · 2023Review
- Evidential deep learning for trustworthy prediction of enzyme commission number.Briefings in bioinformatics · 2023Article
- Functional polyamine metabolic enzymes and pathways encoded by the virosphere.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Elucidating the functional roles of prokaryotic proteins using big data and artificial intelligence.FEMS microbiology reviews · 2023Review
- Trait-Based Method of Quantitative Assessment of Ecological Functional Groups in the Human Intestinal Microbiome.Biology · 2023Article
- Incompatibility and Interchangeability in Molecular Evolution.Genome biology and evolution · 2023Review
- Chemometrics and genome mining reveal an unprecedented family of sugar acid-containing fungal nonribosomal cyclodepsipeptides.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
31 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
backgroundEvolutionarily unrelated proteins that catalyze the same biochemical reactions are often referred to as analogous - as opposed to homologous - enzymes. The existence of numerous alternative, non-homologous enzyme isoforms presents an interesting evolutionary problem; it also complicates genome-based reconstruction of the metabolic pathways in a variety of organisms. In 1998, a systematic search for analogous enzymes resulted in the identification of 105 Enzyme Commission (EC) numbers that included two or more proteins without detectable sequence similarity to each other, including 34 EC nodes where proteins were known (or predicted) to have distinct structural folds, indicating independent evolutionary origins. In the past 12 years, many putative non-homologous isofunctional enzymes were identified in newly sequenced genomes. In addition, efforts in structural genomics resulted in a vastly improved structural coverage of proteomes, providing for definitive assessment of (non)homologous relationships between proteins.
resultsWe report the results of a comprehensive search for non-homologous isofunctional enzymes (NISE) that yielded 185 EC nodes with two or more experimentally characterized - or predicted - structurally unrelated proteins. Of these NISE sets, only 74 were from the original 1998 list. Structural assignments of the NISE show over-representation of proteins with the TIM barrel fold and the nucleotide-binding Rossmann fold. From the functional perspective, the set of NISE is enriched in hydrolases, particularly carbohydrate hydrolases, and in enzymes involved in defense against oxidative stress.
conclusionsThese results indicate that at least some of the non-homologous isofunctional enzymes were recruited relatively recently from enzyme families that are active against related substrates and are sufficiently flexible to accommodate changes in substrate specificity.
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