Get access

Function-based assessment of structural similarity measurements using metal co-factor orientation

Authors

  • Stefan Senn,

    Corresponding author
    1. Environmental Biophysics and Molecular Ecology Program, Institute of Marine and Coastal Sciences, Rutgers University, New Brunswick, New Jersey
    • Correspondence to: Yana Bromberg; Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, 76 Lipman Drive, NJ 08901. E-mail: yana@bromberglab.org or Stefan Senn. E-mail: senn@marine.rutgers.edu

    Search for more papers by this author
  • Vikas Nanda,

    1. Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey
    Search for more papers by this author
  • Paul Falkowski,

    1. Environmental Biophysics and Molecular Ecology Program, Institute of Marine and Coastal Sciences, Rutgers University, New Brunswick, New Jersey
    2. Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey
    3. Department Environmental Sciences, Rutgers University, New Brunswick, New Jersey
    4. Department of Earth and Planetary Sciences, Rutgers University, Piscataway, New Jersey
    Search for more papers by this author
  • Yana Bromberg

    Corresponding author
    1. Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey
    • Correspondence to: Yana Bromberg; Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, 76 Lipman Drive, NJ 08901. E-mail: yana@bromberglab.org or Stefan Senn. E-mail: senn@marine.rutgers.edu

    Search for more papers by this author

ABSTRACT

Structure comparison is widely used to quantify protein relationships. Although there are several approaches to calculate structural similarity, specifying significance thresholds for similarity metrics is difficult due to the inherent likeness of common secondary structure elements. In this study, metal co-factor location is used to assess the biological relevance of structural alignments. The distance between the centroids of bound co-factors adds a chemical and function-relevant constraint to the structural superimposition of two proteins. This additional dimension can be used to define cut-off values for discriminating valid and spurious alignments in large alignment sets. The hypothesis underlying our approach is that metal coordination sites constrain structural evolution, thus revealing functional relationships between distantly related proteins. A comparison of three related nitrogenases shows the sequence and fold constraints imposed on the protein structures up to 18 Å away from the centers of their bound metal clusters. Proteins 2014; 82:648–656. © 2013 Wiley Periodicals, Inc.

Ancillary