ArticleNucleic acids research2010
Modular architecture of nucleotide-binding pockets.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Emerging enzymatic strategies for the synthesis of α-tertiary amino acids.Communications chemistry · 2026Review
- On the evolution of protein-adenine binding.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- An Ancient Fingerprint Indicates the Common Ancestry of Rossmann-Fold Enzymes Utilizing Different Ribose-Based Cofactors.PLoS biology · 2016Article
- Nucleotide binding database NBDB--a collection of sequence motifs with specific protein-ligand interactions.Nucleic acids research · 2016Article
- Exploring Human Diseases and Biological Mechanisms by Protein Structure Prediction and Modeling.Advances in experimental medicine and biology · 2016Article
- Article
- Defining structural and evolutionary modules in proteins: a community detection approach to explore sub-domain architecture.BMC structural biology · 2013Article
- Nucleos: a web server for the identification of nucleotide-binding sites in protein structures.Nucleic acids research · 2013Article
- Identification of binding pockets in protein structures using a knowledge-based potential derived from local structural similarities.BMC bioinformatics · 2012Article
- Identification of nucleotide-binding sites in protein structures: a novel approach based on nucleotide modularity.PloS one · 2012Article
- Phosfinder: a web server for the identification of phosphate-binding sites on protein structures.Nucleic acids research · 2011Article
- Engineering a novel c-di-GMP-binding protein for biofilm dispersal.Environmental microbiology · 2011Article
- Phosphate binding sites identification in protein structures.Nucleic acids research · 2011Article
- The Vein Patterning 1 (VEP1) gene family laterally spread through an ecological network.PloS one · 2011Article
- The Mycobacterium tuberculosis drugome and its polypharmacological implications.PLoS computational biology · 2010Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, modularity has emerged as a general attribute of complex biological systems. This is probably because modular systems lend themselves readily to optimization via random mutation followed by natural selection. Although they are not traditionally considered to evolve by this process, biological ligands are also modular, being composed of recurring chemical fragments, and moreover they exhibit similarities reminiscent of mutations (e.g. the few atoms differentiating adenine and guanine). Many ligands are also promiscuous in the sense that they bind to many different protein folds. Here, we investigated whether ligand chemical modularity is reflected in an underlying modularity of binding sites across unrelated proteins. We chose nucleotides as paradigmatic ligands, because they can be described as composed of well-defined fragments (nucleobase, ribose and phosphates) and are quite abundant both in nature and in protein structure databases. We found that nucleotide-binding sites do indeed show a modular organization and are composed of fragment-specific protein structural motifs, which parallel the modular structure of their ligands. Through an analysis of the distribution of these motifs in different proteins and in different folds, we discuss the evolutionary implications of these findings and argue that the structural features we observed can arise both as a result of divergence from a common ancestor or convergent evolution.
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