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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Main Authors:	Valasatava, Yana, Andreini, Claudia, Rosato, Antonio
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377587/

id	pubmed-4377587
recordtype	oai_dc
spelling	pubmed-43775872015-04-07 Hidden relationships between metalloproteins unveiled by structural comparison of their metal sites Valasatava, Yana Andreini, Claudia Rosato, Antonio 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 MetalS2 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/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Valasatava, Yana Andreini, Claudia Rosato, Antonio
spellingShingle	Valasatava, Yana Andreini, Claudia Rosato, Antonio Hidden relationships between metalloproteins unveiled by structural comparison of their metal sites
author_facet	Valasatava, Yana Andreini, Claudia Rosato, Antonio
author_sort	Valasatava, Yana
title	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_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_sort	hidden relationships between metalloproteins unveiled by structural comparison of their metal sites
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 MetalS2 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.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377587/
_version_	1613204919741841408

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

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