Localization of Protein-Binding Sites Within Families of Proteins

Protein Sci. 2005 Sep;14(9):2350-60. doi: 10.1110/ps.051571905. Epub 2005 Aug 4.


We address the question of whether or not the positions of protein-binding sites on homologous protein structures are conserved irrespective of the identities of their binding partners. First, for each domain family in the Structural Classification of Proteins (SCOP), protein-binding sites are extracted from our comprehensive database of structurally defined binary domain interactions (PIBASE). Second, the binding sites within each family are superposed using a structural alignment of its members. Finally, the degree of localization of binding sites within each family is quantified by comparing it with localization expected by chance. We found that 72% of the 1847 SCOP domain families in PIBASE have binding sites with localization values greater than expected by chance. Moreover, 554 (30%) of these families have localizations that are statistically significant (i.e., more than four standard deviations away from the mean expected by chance). In contrast, only 144 (8%) families have significantly low localization. The absence of a significant correlation of the binding site localization with the average sequence and structural conservations in a family suggests that localization can be helpful for describing the functional diversity of protein-protein interactions, complementing measures of sequence and structural conservation. Consideration of the binding site localization may also result in spatial restraints for the modeling of protein assembly structures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acyl-CoA Dehydrogenase / chemistry
  • Acyl-CoA Dehydrogenase / metabolism
  • Binding Sites
  • Computational Biology / methods*
  • Databases, Protein
  • Evolution, Molecular
  • Lectins, C-Type / chemistry
  • Lectins, C-Type / metabolism
  • Models, Molecular
  • Protein Conformation
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / metabolism*


  • Lectins, C-Type
  • Proteins
  • Acyl-CoA Dehydrogenase