Finding evolutionary relations beyond superfamilies: Fold-based superfamilies

Keiko Matsuda, Takaaki Nishioka, Kengo Kinoshita, Takeshi Kawabata, Nobuhiro Go

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Superfamily classifications are based variably on similarity of sequences, global folds, local structures, or functions. We have examined the possibility of defining superfamilies purely from the viewpoint of the global fold/function relationship. For this purpose, we first classified protein domains according to the β-sheet topology. We then introduced the concept of kinship relations among the classified β-sheet topology by assuming that the major elementary event leading to creation of a new β-sheet topology is either an addition or deletion of one β-strand at the edge of an existing β-sheet during the molecular evolution. Based on this kinship relation, a network of protein domains was constructed so that the distance between a pair of domains represents the number of evolutionary events that lead one from the other domain. We then mapped on it all known domains with a specific core chemical function (here taken, as an example, that involving ATP or its analogs). Careful analyses revealed that the domains are found distributed on the network as >20 mutually disjointed clusters. The proteins in each cluster are defined to form a fold-based superfamily. The results indicate that >20 ATP-binding protein superfamilies have been invented independently in the process of molecular evolution, and the conservative evolutionary diffusion of global folds and functions is the origin of the relationship between them.

Original languageEnglish
Pages (from-to)2239-2251
Number of pages13
JournalProtein Science
Issue number10
Publication statusPublished - 2003 Oct 1


  • ATP-binding domains
  • Kinship relations of global folds
  • Purine biosynthesis
  • Structure/function relationship


Dive into the research topics of 'Finding evolutionary relations beyond superfamilies: Fold-based superfamilies'. Together they form a unique fingerprint.

Cite this