title: Comprehensive structural classification of ligand-binding motifs in proteins.
abstract: Comprehensive knowledge of protein-ligand interactions should provide a useful basis for annotating protein functions, studying protein evolution, engineering enzymatic activity, and designing drugs. To investigate the diversity and universality of ligand-binding sites in protein structures, we conducted the all-against-all atomic-level structural comparison of over 180,000 ligand-binding sites found in all the known structures in the Protein Data Bank by using a recently developed database search and alignment algorithm. By applying a hybrid top-down-bottom-up clustering analysis to the comparison results, we determined approximately 3000 well-defined structural motifs of ligand-binding sites. Apart from a handful of exceptions, most structural motifs were found to be confined within single families or superfamilies, and to be associated with particular ligands. Furthermore, we analyzed the components of the similarity network and enumerated more than 4000 pairs of structural motifs that were shared across different protein folds.
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan. akinjo@protein.osaka-u.ac.jp
authors.forename: Akira R
authors.initials: AR
authors.lastname: Kinjo
authors.forename: Haruki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D016000:Cluster Analysis; D008024:Ligands; D053858:Metabolic Networks and Pathways / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D005810:Multigene Family; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs / Q000502:physiology*; D011506:Proteins / Q000737:chemistry* / Q000145:classification*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011506:Proteins