Quantum chemical studies of biochemical reaction mechanisms
Title: |
Quantum chemical studies of biochemical reaction mechanisms |
DNr: |
SNIC 2017/1-590 |
Project Type: |
SNIC Medium Compute |
Principal Investigator: |
Margareta Blomberg <margareta.blomberg@su.se> |
Affiliation: |
Stockholms universitet |
Duration: |
2018-01-01 – 2019-01-01 |
Classification: |
10407 |
Keywords: |
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Abstract
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 (Density Functional Theory, DFT)
are used to study biochemical model systems. Our group is world
leading in this field, and our approach to quantum biomodeling is
generally adopted as an important tool, as can be seen from the large
number of citations (530) of an early (2000) description of this
approach, as well as the 155 citations of a more recent review (2014). My main project concerns mechanisms for reduction of
molecular oxygen and proton pumping in cytochrome c oxidase (CcO), the
terminal enzyme in the respiratory chain where oxygen is reduced to
water. We have suggested a gating mechanism for proton pumping against
the gradient, which can explain many important experimental
observations, and which is now further developed based on continued
DFT calculations on larger and better models. Another enzyme of
particular interest is nitric oxide reductase (NOR), since it has
large similarities to cytochrome c oxidase. The first crystal
structure of this enzyme was solved in 2010. Based on DFT calculations
on the active site taken from the crystal structure, we have suggested
a reaction mechanisms of NOR, which also can explain why this enzyme
is non-electrogenic. CcO and NOR belong to the same family of enzymes and certain species 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. Recently we published a mechanism for oxygen reduction in NOR. At present calculations are performed for NO reduction in CcO. During last year I started closer collaborations with the experimental groups working on these enzymes at Stockholm University, which has turned out to be very fruitful.