D21 - Metalloenzymes and Chemical Biomimetics

COST Action D21 was conceived with the aim of increasing the knowledge of the chemistry of metal sites in proteins to strengthen their application to chemical, biotechnological, pharmacological and environmental sciences. Among others, significant achievements of Action D21 are the systematic investigation of the human heme peroxidase family, which has established the complete array of reactive oxidants that mediate halogenation, nitr(osyl)ation and oxidation of cellular components such as lipids and proteins. These reactions explain the potential to inflict tissue damage and to induce inflammation, and their better characterisation will facilitate the development of drugs targeted to diseases such as cardiovascular disease, neurodegenerative disorders and asthma. In parallel, the engineering and biophysical studies on a broad set of plant heme peroxidases have provided a full account of the specific structural effects ruling the activity of the enzymes, the clarification of their catalytic mechanism, and have opened new applications in biotechnology as well as in the industrial and medical applications of these enzymes. The field of protein-protein interactions has gained an important advancement by the development of new computational algorithms that, in combination with experimental techniques, allow to understand at a molecular level the structural basis of the specificity of inter-protein interactions. The programme has been made available to the scientific community on request.

The study of biomimetic model compounds has enabled to dissect the steps involved in the pathway of enzymatic oxidation by tyrosinase, the enzyme responsible for tissue melanization, and reproduce the chemistry exhibited by other metal oxygenases, oxidases and catalases. In addition, the direct observation of enzyme-inhibitor complexes through sophisticated spectroscopic techniques has clarified the mechanism of interaction of the small molecules at the active site of tyrosinase.

Important progress has been made on the way in which redox proteins/enzymes function and how their properties can be modified. Immobilization on solid supports with new techniques has allowed a literally close look at the immobilized bio-molecules. A detailed understanding of how a single enzyme works is within reach and will provide additional valuable information over the knowledge that can be gained from studies on statistically large ensembles of molecules. D21 has coordinated the collaboration of 110 research groups from 20 different countries. The obtained scientific results have been disseminated through a large number of workshops and meetings as well as by the publication of a very large number of articles in prestigeous peer reviewed journals.