Cel Recently, the discovery of new antibiotics has slowed, while the incidences of infections caused by bacteria that have become resistant to commonly used antibiotics are rising. There is therefore a growing clinical need for innovative approaches to developing novel anti-infective compounds. Hydrogen is an important energy substrate for a number of pathogenic bacteria and H2 oxidation is essential for the virulence of Salmonella enterica serovar Typhimurium. S. enterica expresses three different H2-uptake [NiFe]-hydrogenases and one of these (termed hydrogenase-5) belongs to a novel class of O2-tolerant hydrogenases that is synthesized aerobically and oxidizes H2 in the presence of O2. The Hyd-5 gene cluster encodes two accessory proteins, HydH and HydG, that are absent in anaerobic systems and are conserved in those systems in which hydrogenases are synthesized in the presence of oxygen. In other systems, HydH homologs have been proposed as scaffolding proteins that bind the immature [NiFe] cofactor prior its transfer to the large subunit of the enzyme. HydG-like proteins are hypothesised to assemble or stabilize the Fe-S clusters of small subunit during biosyntheis. This proposal aims to study the functional role of accessory proteins HydH and HydG in the biosynthesis of Hyd-5 and to design novel small molecule compounds that potentially inhibit hydrogenase activity and assembly. Understanding the mechanisms involved in the biosynthesis of Hyd-5 will allow the development of hydrogenase inhibitors and, as consequence, anti-infectives of virulence of Salmonella and other bacterial pathogens. This project addresses a key biomedical challenge and establishes [NiFe] hydrogenases as novel and credible drug targets. Dziedzina nauki natural sciencesbiological sciencesmicrobiologybacteriologynatural scienceschemical scienceselectrochemistryelectrolysismedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsengineering and technologyenvironmental engineeringenergy and fuelsfuel cellsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Słowa kluczowe [NiFe]-hydrogenase oxygen tolerance Salmonella hydrogen protein-protein interaction [NiFe] cofactor Fe-S cluster inhibitor Program(-y) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Temat(-y) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Zaproszenie do składania wniosków H2020-MSCA-IF-2014 Zobacz inne projekty w ramach tego zaproszenia System finansowania MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Koordynator UNIVERSITY OF DUNDEE Wkład UE netto € 183 454,80 Adres Nethergate DD1 4HN Dundee Zjednoczone Królestwo Zobacz na mapie Region Scotland Eastern Scotland Angus and Dundee City Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 183 454,80