Zinc metalloproteins are involved in many biological processes and play crucial biochemical roles across all domains of life. Local structure around the zinc ion, especially the coordination geometry (CG), is dictated by the protein sequence and is often directly related to the function of the protein. Current methodologies in characterizing zinc metalloproteins' CG consider only previously reported CG models based mainly on nonbiological chemical context. Exceptions to these canonical CG models are either misclassified or discarded as "outliers." Thus, we developed a less-biased method that directly handles potential exceptions without pre-assuming any CG model. Our study shows that numerous exceptions could actually be further classified and that new CG models are needed to characterize them. Also, these new CG models are cross-validated by strong correlation between independent structural and functional annotation distance metrics, which is partially lost if these new CGs models are ignored. Furthermore, these new CG models exhibit functional propensities distinct from the canonical CG models.

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Published in Proteins: Structure, Function, and Bioinformatics, v. 83, no. 8, p. 1470-1487.

© 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

This is an open access article under the terms of the Creative Commons Attribution- NonCommercial License which permits use, distribution and reproduction in any medium, provided that the Contribution is properly cited and is not used for commercial purposes.

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National Science Foundation; Grant number: NSF 1252893 (to H.N.B.M.); Grant sponsor: NIH; Grant numbers: P01CA163223-01A1 (to A.N.L. and T.W.-M.F.); 1U24DK097215-01A1 (to R.M.H., T.W.-M.F., A.N.L., and H.N.B.M.); P20GM103436 (to E.C.R.; Nigel Cooper, PI); Grant sponsor: Nigel Cooper, PI.

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