Metal binding sites in macromolecular structures

University Of Virginia, Charlottesville VA

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Abstract

Project: Metal binding environments in macromolecular structures Abstract: Metal ions play vital roles in both the mechanism and architecture of biological macromolecules, including the catalysis of biochemical reactions, electron transport, binding of gases, and stabilization of nucleotides and other polyphosphate compounds. However, a recent survey of publicly available structures of metal-containing proteins and nucleic acids deposited in the PDB revealed an abundance of misidentified and/or sub-optimally modeled metal binding sites. This prompted the creation of a diagnostic tool for the models of metal binding microenvironments, the CheckMyMetal (CMM) web server (http://csgid.org/csgid/metal_sites/), which detects geometric and other irregularities in structures of metal binding sites and alerts researchers to potential errors in metal assignment. As the production version of CMM has gained widespread usage, the research community has identified several directions for future development of major interest:1) investigate and validate uncommon heavy metal binding sites in macromolecular structures; 2) establish a server to provide customized subsets of high-quality, validated metal binding sites; 3) develop tools to automatically detect likely metal binding sites in electron density, and identify and add the most probable metal ion during crystallographic model building and refinement; and 4) systematically catalog metal binding architectures and detect new metal binding motifs. The toolkit we propose to develop, using CMM as a basis, contains several modules that will work either independently or as integrated steps in the structure modeling, validation, interpretation and annotation pipeline. This proposal was designed not only for structural biologists to model and validate new structures during crystallographic model building and refinement, but also for a broader audience?biomedical researchers studying metal-containing proteins and nucleic acids.