Hyunho KimPhD student
About me
Graduated from the chemistry program in Technical University of Munich (TUM) with focus on organic chemistry and biochemistry. Currently I am interested in cellular bioenergetic processes, ranging from the aerobic mitochondrial respiratory chain to sodium-driven anaerobic respiration at thermodynamic limit of life. We use multi-scale computational methods, such as atomistic molecular dynamics (MD) simulations, quantum mechanical (QM) calculations, as well as hybrid molecular and quantum mechanics methods (QMMM) to study biological systems.
Room Number: A571a
Research group: Ville Kaila
BSc in Chemistry at Technical University of Munich
Msc in Organic Chemistry and Biochemistry at Technical University of Munich
PhD in Department of Biochemistry and Biophysics at Stockholm University
Publications
A selection from Stockholm University publication database
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Quinone Catalysis Modulates Proton Transfer Reactions in the Membrane Domain of Respiratory Complex I
2023. Hyunho Kim (et al.). Journal of the American Chemical Society 145 (31), 17075-17086
ArticleRead more about Quinone Catalysis Modulates Proton Transfer Reactions in the Membrane Domain of Respiratory Complex IComplex I is a redox-driven proton pump that drives electron transport chains and powers oxidative phosphorylation across all domains of life. Yet, despite recently resolved structures from multiple organisms, it still remains unclear how the redox reactions in Complex I trigger proton pumping up to 200 Å away from the active site. Here, we show that the proton-coupled electron transfer reactions during quinone reduction drive long-range conformational changes of conserved loops and trans-membrane (TM) helices in the membrane domain of Complex I from Yarrowia lipolytica. We find that the conformational switching triggers a π → α transition in a TM helix (TM3ND6) and establishes a proton pathway between the quinone chamber and the antiporter-like subunits, responsible for proton pumping. Our large-scale (>20 μs) atomistic molecular dynamics (MD) simulations in combination with quantum/classical (QM/MM) free energy calculations show that the helix transition controls the barrier for proton transfer reactions by wetting transitions and electrostatic effects. The conformational switching is enabled by re-arrangements of ion pairs that propagate from the quinone binding site to the membrane domain via an extended network of conserved residues. We find that these redox-driven changes create a conserved coupling network within the Complex I superfamily, with point mutations leading to drastic activity changes and mitochondrial disorders. On a general level, our findings illustrate how catalysis controls large-scale protein conformational changes and enables ion transport across biological membranes.