Molego-based definition of the architecture and specificity of metal-binding sites

Catherine H. Schein, Bin Zhou, Numan Oezguen, Venkatarajan S. Mathura, Werner Braun

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Decomposing proteins into "molegos," building blocks that are conserved in sequence and 3D-structure, can identify functional elements. To demonstrate the specificity of the decomposition method, the PCPMer program suite was used to numerically define physical chemical property motifs corresponding to the molegos that make up the metal-containing active sites of three distinct enzyme families, from the dimetallic phosphatases, DNase 1 related nucleases/phosphatases, and dioxygenases. All three superfamilies bind metal ions in a β-strand core region but differ in the number and type of ions needed for activity. The motifs were then used to automatically identify proteins in the ASTRAL40 database that contained similar motifs. The proteins with the highest PCPMer score in the database were primarily metal-binding enzymes that were related in function to those in the alignment used to generate the PCPMer motif lists. The proteins that contained motifs similar to the dioxygenases differed from those found with PCP-motifs for phosphatases and nucleases. Relatively few metal-binding enzymes were detected when the search was done with PCP-motifs defined for interleukin-1 related proteins, which have a O-strand core but do not bind metal ions. While the box architecture was constant in each superfamily, the specificity for the metal ion preferred for enzymatic activity is determined by the pattern of carbonyl, hydroxyl or imadazole groups in key positions in the molegos. These results have implications for the design of metal-binding enzymes, and illustrate the ability of the PCPMer approach to distinguish, at the sequence level, structural and functional elements.

Original languageEnglish (US)
Pages (from-to)200-210
Number of pages11
JournalProteins: Structure, Function and Genetics
Issue number1
StatePublished - Jan 1 2005
Externally publishedYes


  • DNase 1 superfamily
  • Dimetallic phosphatases
  • Dioxygenases
  • Identifying functional homologues
  • Interleukin-1 structural family
  • Metal ion catalysis
  • PCPMer
  • Protein design
  • Total sequence decomposition

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology


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