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Hidden relationships between metalloproteins unveiled by structural comparison of their metal sites

Metalloproteins account for a substantial fraction of all proteins. They incorporate metal atoms, which are required for their structure and/or function. Here we describe a new computational protocol to systematically compare and classify metal-binding sites on the basis of their structural similari...

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Autores principales: Valasatava, Yana, Andreini, Claudia, Rosato, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377587/
https://www.ncbi.nlm.nih.gov/pubmed/25820752
http://dx.doi.org/10.1038/srep09486
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author Valasatava, Yana
Andreini, Claudia
Rosato, Antonio
author_facet Valasatava, Yana
Andreini, Claudia
Rosato, Antonio
author_sort Valasatava, Yana
collection PubMed
description Metalloproteins account for a substantial fraction of all proteins. They incorporate metal atoms, which are required for their structure and/or function. Here we describe a new computational protocol to systematically compare and classify metal-binding sites on the basis of their structural similarity. These sites are extracted from the MetalPDB database of minimal functional sites (MFSs) in metal-binding biological macromolecules. Structural similarity is measured by the scoring function of the available MetalS(2) program. Hierarchical clustering was used to organize MFSs into clusters, for each of which a representative MFS was identified. The comparison of all representative MFSs provided a thorough structure-based classification of the sites analyzed. As examples, the application of the proposed computational protocol to all heme-binding proteins and zinc-binding proteins of known structure highlighted the existence of structural subtypes, validated known evolutionary links and shed new light on the occurrence of similar sites in systems at different evolutionary distances. The present approach thus makes available an innovative viewpoint on metalloproteins, where the functionally crucial metal sites effectively lead the discovery of structural and functional relationships in a largely protein-independent manner.
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spelling pubmed-43775872015-04-07 Hidden relationships between metalloproteins unveiled by structural comparison of their metal sites Valasatava, Yana Andreini, Claudia Rosato, Antonio Sci Rep Article Metalloproteins account for a substantial fraction of all proteins. They incorporate metal atoms, which are required for their structure and/or function. Here we describe a new computational protocol to systematically compare and classify metal-binding sites on the basis of their structural similarity. These sites are extracted from the MetalPDB database of minimal functional sites (MFSs) in metal-binding biological macromolecules. Structural similarity is measured by the scoring function of the available MetalS(2) program. Hierarchical clustering was used to organize MFSs into clusters, for each of which a representative MFS was identified. The comparison of all representative MFSs provided a thorough structure-based classification of the sites analyzed. As examples, the application of the proposed computational protocol to all heme-binding proteins and zinc-binding proteins of known structure highlighted the existence of structural subtypes, validated known evolutionary links and shed new light on the occurrence of similar sites in systems at different evolutionary distances. The present approach thus makes available an innovative viewpoint on metalloproteins, where the functionally crucial metal sites effectively lead the discovery of structural and functional relationships in a largely protein-independent manner. Nature Publishing Group 2015-03-30 /pmc/articles/PMC4377587/ /pubmed/25820752 http://dx.doi.org/10.1038/srep09486 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Valasatava, Yana
Andreini, Claudia
Rosato, Antonio
Hidden relationships between metalloproteins unveiled by structural comparison of their metal sites
title Hidden relationships between metalloproteins unveiled by structural comparison of their metal sites
title_full Hidden relationships between metalloproteins unveiled by structural comparison of their metal sites
title_fullStr Hidden relationships between metalloproteins unveiled by structural comparison of their metal sites
title_full_unstemmed Hidden relationships between metalloproteins unveiled by structural comparison of their metal sites
title_short Hidden relationships between metalloproteins unveiled by structural comparison of their metal sites
title_sort hidden relationships between metalloproteins unveiled by structural comparison of their metal sites
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377587/
https://www.ncbi.nlm.nih.gov/pubmed/25820752
http://dx.doi.org/10.1038/srep09486
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