Aberrant coordination geometries discovered in the most abundant metalloproteins

Sen Yao, Robert M. Flight, Eric C. Rouchka, Hunter N.B. Moseley

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Metalloproteins bind and utilize metal ions for a variety of biological purposes. Due to the ubiquity of metalloprotein involvement throughout these processes across all domains of life, how proteins coordinate metal ions for different biochemical functions is of great relevance to understanding the implementation of these biological processes. Toward these ends, we have improved our methodology for structurally and functionally characterizing metal binding sites in metalloproteins. Our new ligand detection method is statistically much more robust, producing estimated false positive and false negative rates of ∼0.11% and ∼1.2%, respectively. Additional improvements expand both the range of metal ions and their coordination number that can be effectively analyzed. Also, the inclusion of additional quality control filters has significantly improved structure-function Spearman correlations as demonstrated by rho values greater than 0.90 for several metal coordination analyses and even one rho value above 0.95. Also, improvements in bond-length distributions have revealed bond-length modes specific to chemical functional groups involved in multidentation. Using these improved methods, we analyzed all single metal ion binding sites with Zn, Mg, Ca, Fe, and Na ions in the wwPDB, producing statistically rigorous results supporting the existence of both a significant number of unexpected compressed angles and subsequent aberrant metal ion coordination geometries (CGs) within structurally known metalloproteins. By recognizing these aberrant CGs in our clustering analyses, high correlations are achieved between structural and functional descriptions of metal ion coordination. Moreover, distinct biochemical functions are associated with aberrant CGs versus nonaberrant CGs. Proteins 2017; 85:885–907.

Original languageEnglish
Pages (from-to)885-907
Number of pages23
JournalProteins: Structure, Function and Bioinformatics
Issue number5
StatePublished - May 1 2017

Bibliographical note

Funding Information:
The authors have no conflict of interest with this work. The contents of this work are solely the responsibility of the authors and do not represent the official views of the NIH or the National Institute for General Medical Sciences (NIGMS).

Publisher Copyright:
© 2017 The Authors Proteins: Structure, Function and Bioinformatics Published by Wiley Periodicals, Inc.


  • 3D structure
  • bidentation
  • compressed angle
  • structural bioinformatics
  • structure-function relationship

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology


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