Biochemistry of heme Q
- Lebensmittel, Ernährung, Gesundheit
- Biotechnologie
Abstract
Recently, a novel heme b biosynthesis pathway has been detected in Gram-positive bacteria with the last step being catalysed by HemQ, an enzyme that is not found in human metabolism. Despite of its importance there is only little knowledge about its biochemistry and the mechanism of its action is completely unknown. Thus this basic research project focuses on the elucidation of structure-function relationships of HemQ. By applying a broad set of biochemical and biophysical techniques this interdisciplinary project aims at investigating four model proteins from different phylogenetic lineages in order to establish a general reaction mechanism. In detail we have selected three HemQs from important human pathogens, namely Listeria monocytogenes, Staphylococcus aureus and Corynebacterium diphteriae, thus including dangerous (antibiotics-resistant) and wide-spread hospital bugs. Additionally, HemQ from the Archaeum Sulfolobus sulfataricus will be investigated. The model proteins will be produced recombinantly, mutated and analysed in a comprehensive and comparative biochemical study including biospectroscopies, kinetic, thermodynamic and redox studies, X-ray crystallography and computational methods. Based on the obtained knowledge of action of HemQ at a molecular basis, it will be possible to rationally design inhibitors against HemQ in the future. Consequently, this study will later on allow to create a new class of antibiotics against these wide-spread pathogens. These bacteria are strongly dependent on the function of many heme-containing enzymes including those that are directly involved in host attack. Thus inhibition of heme biosynthesis will immediately block the viability of these pathogens.
www.icpp-spp.orgProject staff
Paul Georg Furtmüller
ao.Univ.Prof. Dipl.-Ing.Dr.nat.techn. Paul Georg Furtmüller
paul.furtmueller@boku.ac.at
Tel: +43 1 47654-77277
Project Leader
01.11.2016 - 02.11.2016
Stefan Hofbauer
Ass.Prof. Priv.-Doz. Dipl.-Ing. Stefan Hofbauer Ph.D.
stefan.hofbauer@boku.ac.at
Tel: +43 1 47654-77258
Project Leader
03.11.2016 - 31.10.2021
BOKU partners
