Quantum chemical studies of biochemical reaction mechanisms
Title: Quantum chemical studies of biochemical reaction mechanisms
SNIC Project: SNIC 2020/5-655
Project Type: SNIC Medium Compute
Principal Investigator: Margareta Blomberg <margareta.blomberg@su.se>
Affiliation: Stockholms universitet
Duration: 2021-01-01 – 2022-01-01
Classification: 10407


The general goal of my research is to elucidate enzyme mechanisms, in particular for redox active enzymes containing transition metals. For this purpose quantum chemical methods (mainly hybrid Density Functional Theory, DFT) are used to study biochemical model systems. My main project concerns mechanisms for enzymes involved in cellular respiration. Therefore I study the reduction of molecular oxygen and proton pumping in cytochrome c oxidase (CcO), the terminal enzyme in the respiratory chain. Another enzyme belonging to the same family as CcO is nitric oxide reductase (cNOR), which reduces nitric oxide to nitrous oxide and water. The basic mechanisms for both these enzymes have been studied, and several new mechanistic aspects have been established in several publications. Furthermore, certain species of CcO and cNOR can use both substrates, molecular oxygen and nitric oxide as substrate. An important approach to learn more about the reaction mechanisms is to make comparisons between the two enzymes for both substrates. In recent years I have developed closer collaborations with the experimental groups working on these enzymes at Stockholm University, which has turned out to be very fruitful and resulted in several publications, and which will continue. A newer aspect in the project is to study isotope effects in the formation of nitrous oxide, comparing different sources, such as cNOR and p450NOR. This is important in tracing the different sources for release into the atmosphere of the greenhouse gas nitrous oxide. In this part of the project I am cooperating with researchers at the EMPA institute belonging to ETH in Zurich. I will also study mechanisms of other enzymes forming nitrous oxide from nitric oxide, such as flavindiiron NO reductases (FNOR) and hydroxyl amine oxidases (HAO).