Peroxid reaktivitet till Myoglobin: förstå reaktiva intermediärer från röntgen-spektroskopi

Tidsperiod: 2020-01-01 till 2022-12-31

Projektledare: Meiyuan Guo

Finansiär: Vetenskapsrådet

Bidragstyp: Bidrag för anställning eller stipendier

Budget: 3 150 000 SEK

The important role of globins to human health has attracted a large body of research. However, the existing research does not emphasize the fundamental redox chemistry and identify the early-time intermediates in the globin peroxidative reaction cycles - which pose a significant risk to human health. The proposed research aims to study the peroxidative reaction pathways in globin and characterize the intermediates throughout the processes. We propose to utilize multiple of X-ray spectroscopy methods combining a newly developed microfluidic continuous mixing device for in-situ measurements of the peroxidative reaction on the millisecond time scale. The proposal intends to follow the reaction kinetics of H2O2 binding to the Fe-containing active site of met-myoglobin and at room temperature and investigate the effect of acidic/basic condition to the reaction pathway and intermediate selectivity, and study the reaction kinetics and mechanism of H2O2 binding to oxy-myoglobin at room temperature and anerobic conditions. The research will be conducted at SLAC National Accelerator Laboratory/Stanford University for two years (out-going phase) and then continued at Department of Physics and Astronomy/Uppsala University for the remaining year (returning phase).Successful implementation of this project will provide unprecedented data for ligand reaction and binding to proteins under real conditions and open the opportunity to access intermediates that are otherwise inaccessible.