title: A less-biased analysis of metalloproteins reveals novel zinc coordination geometries.
abstract: 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.
authors.affiliation: School of Interdisciplinary and Graduate Studies, University of Louisville, Louisville, Kentucky, 40292.|Department of Computer Engineering and Computer Science, University of Louisville, Louisville, Kentucky, 40292.
authors.forename: Sen
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, 40356.|Markey Cancer Center, University of Kentucky, Lexington, Kentucky, 40356.|Center for Environmental and Systems Biochemistry, University of Kentucky, Lexington, Kentucky, 40356.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Flight
authors.affiliation: School of Interdisciplinary and Graduate Studies, University of Louisville, Louisville, Kentucky, 40292.|Department of Computer Engineering and Computer Science, University of Louisville, Louisville, Kentucky, 40292.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Rouchka
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, 40356.|Markey Cancer Center, University of Kentucky, Lexington, Kentucky, 40356.|Center for Environmental and Systems Biochemistry, University of Kentucky, Lexington, Kentucky, 40356.
authors.forename: Hunter N B
authors.initials: HN
authors.lastname: Moseley
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008667:Metalloproteins; D015032:Zinc
keywords: 3D structure; bidentation; carboxylate shift; compressed angle; structural bioinformatics; structure-function relationship