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 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

FindGeo: a tool for determining metal coordination geometry.

Abstract Summary: Metals are essential for the structure and function of many proteins and nucleic acids. The geometrical arrangement of the atoms that coordinate a metal in a biological macromolecule is an important determinant of the specificity and role of that metal. At present, however, this information can be retrieved only from the literature, which sometimes contains an improper or incorrect description of the geometry, and often lacks it altogether. Thus, we developed FindGeo to quickly and easily determine the coordination geometry of selected, or all, metals in a given structure. FindGeo works by superimposing the metal-coordinating atoms in the input structure to a library of templates with alternative ideal geometries, which are ranked by RMSD to identify the best geometry assignment. Availability: FindGeo is freely available as a web service and as a stand-alone program at http://metalweb.cerm.unifi.it/tools/findgeo/. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

MetalPDB: a database of metal sites in biological macromolecular structures

We present here MetalPDB (freely accessible a

MetalPredator: a web server to predict iron-sulfur cluster binding proteomes.

Abstract Motivation: The prediction of the iron–sulfur proteome is highly desirable for biomedical and biological research but a freely available tool to predict iron–sulfur proteins has not been developed yet. Results: We developed a web server to predict iron–sulfur proteins from protein sequence(s). This tool, called MetalPredator, is able to process complete proteomes rapidly with high recall and precision. Availability and Implementation: The web server is freely available at: http://metalweb.cerm.unifi.it/tools/metalpredator/. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

PF24 and training for teachers: a workshop approach proposal

Universities have a key role in the initial training for teachers, therefore they can contribute to innovate school, e.g. by proposing students-centered teaching. This article presents the chemistry course activated by the University of Florence as part of the PF24 programme. The course presented contents that were inspired by the most advanced research in chemistry teaching through a problem-based and laboratory approach. The course has obtained good results both in terms of interest shown by attendants and objectives achieved. PF24 e formazione docenti: una proposta di approccio laboratorialeLe Università giocano un ruolo essenziale nella formazione iniziale dei docenti, potendo così contribuire al cambiamento della scuola dal suo interno e all’introduzione di didattiche incentrate sugli studenti. In questo articolo si presenta il corso di didattica della chimica attivato dall’Università di Firenze nell’ambito del PF24. Il corso ha presentato contenuti ispirati alla più aggiornata ricerca in didattica della chimica attraverso un approccio problem-based e laboratoriale. Il corso ha ottenuto buoni risultati sia in termini di interesse mostrato dagli studenti frequentanti sia in termini di obiettivi raggiunti

PF24 and training for teachers: a workshop approach proposal

Universities have a key role in the initial training for teachers, therefore they can contribute to innovate school, e.g. by proposing students-centered teaching. This article presents the chemistry course activated by the University of Florence as part of the PF24 programme. The course presented contents that were inspired by the most advanced research in chemistry teaching through a problem-based and laboratory approach. The course has obtained good results both in terms of interest shown by attendants and objectives achieved.   PF24 e formazione docenti: una proposta di approccio laboratoriale Le Università giocano un ruolo essenziale nella formazione iniziale dei docenti, potendo così contribuire al cambiamento della scuola dal suo interno e all’introduzione di didattiche incentrate sugli studenti. In questo articolo si presenta il corso di didattica della chimica attivato dall’Università di Firenze nell’ambito del PF24. Il corso ha presentato contenuti ispirati alla più aggiornata ricerca in didattica della chimica attraverso un approccio problem-based e laboratoriale. Il corso ha ottenuto buoni risultati sia in termini di interesse mostrato dagli studenti frequentanti sia in termini di obiettivi raggiunti

To what extent do structural changes in catalytic metal sites affect enzyme function?

About half of known enzymatic reactions involve metals. Enzymes belonging to the same superfamily often evolve to catalyze different reactions on the same structural scaffold. The work presented here investigates how functional differentiation, within superfamilies that contain metalloenzymes, relates to structural changes at the catalytic metal site. In general, when the catalytic metal site is unchanged across the enzymes of a superfamily, the functional differentiation within the superfamily tends to be low and the mechanism conserved. Conversely, all types of structural changes in the metal binding site are observed for superfamilies with high functional differentiation. Overall, the catalytic role of the metal ions appears to be one of the most conserved features of the enzyme mechanism within metalloenzyme superfamilies. In particular, when the catalytic role of the metal ion does not involve a redox reaction (i.e. there is no exchange of electrons with the substrate), this role is almost always maintained even when the site undergoes significant structural changes. In these enzymes, functional diversification is most often associated with modifications in the surrounding protein matrix, which has changed so much that the enzyme chemistry is significantly altered. On the other hand, in more than 50% of the examples where the metal has a redox role in catalysis, changes at the metal site modify its catalytic role. Further, we find that there are no examples in our dataset where metal sites with a redox role are lost during evolution. SYNOPSIS: In this paper we investigate how functional diversity within superfamilies of metalloenzymes relates to structural changes at the catalytic metal site. Evolution tends to strictly conserve the metal site. When changes occur, they do not modify the catalytic role of non-redox metals whereas they affect the role of redox-active metals