Humboldt-Universität zu Berlin - Structural Biology / Biochemistry


Structural evidence for intermediates during O2 formation in photosystem II (NatureMay'23)

Rana Hussein, Mohamed Ibrahim (present address Inst Mol Medicine, University of Lübeck, Germany) and Holger Dobbek together with Athina Zouni (UniSysCat/SFB1078) in collaboration with colleagues from the Lawrence Berkeley National Laboratory (CA, USA), Uppsala University (Sweden), KTH Royal Inst of Technology  Stockholm, Sweden), RIKEN Spring-8 Center (Hyogo, Japan), SLAC National Acceleratr Laboratory (Menlo Park, CA, USA), UCSF (San Francisco, CA, USA), UC Berkeley (CA, USA), UW Madison (Wisconsin, USA), Umeå University (Umeå, Sweden) used time-resolved crystallography (XFEL) to reveal groundbreaking structural insights into the mechanism of the water oxidation process of PSII during the S3-S0 transition.




Asmit Bhowmick, Rana Hussein, Isabel Bogacz, et al (2023) Nature DOI: 10.1038/s41586-023-06038-z


Discovery of the Lanthipeptide Curvocidin and Structural Insights into its Trifunctional Synthetase CuvL (Angew. Chem. Int. Ed, April '23)

Berta Martins, María González-Viegas and Holger Dobbek together with colleagues from the group of Roderich Süssmuth (UniSysCat, TU Berlin, Germany) used X-ray crystallography and NMR together with other biochemical tools to underline the principles of domain organisation and substrate recruitment of class IV and III lanthipeptide synthases.




Arnar Sigurdsson, Berta M Martins et al., Ang. Int Ed Chem, e202302490, DOI: 10.1002/anie.202302490


Substrate Activation at the Ni,Fe Cluster of CO Dehydrogenases: The Influence of the Protein Matrix (ACS Catalysis, October '22)

Yudhajeet Basak and colleagues analysed several variants of Ni,Fe-CODH and showed that residues in the second coordination sphere of cluster C determine not only substrate activation but also its coordination and stability. The study revealed how precariously the water structure at cluster C depends on the surrounding amino acids and how even seemingly minor changes can destabilise the cluster to the extent that asymmetrically coordinated [Fe4(μ3-S)4] clusters can form, highlighting the plasticity of cluster C.




Yudhajeet Basak, Jae-Hun Jeoung, Lilith Domnik, Jakob Ruickoldt, and Holger Dobbek (2022) ACS Catalysis. 12711. DOI: 10.1021/acscatal.2c02922


Structural basis for coupled ATP-driven electron transfer in the double-cubane cluster protein (PNAS, June '22)

Jae-Hun Jeoung, Sabine Nicklisch and Holger Dobbek conducted binding and kinetics studies in tandem with X-ray crystallography to investigate the spatial arrangements of functional elements necessary for ATP-dependent electron transfer. Striking similarities with the non-homologous nitrogenases suggest a convergent evolution of catalytic strategies to achieve ATP-driven electron transfers between iron-sulphur clusters.




Jae-Hun Jeoung, Sabine Nicklisch and Holger Dobbek (2022) PNAS, 119, e2203576119, DOI:10.1073/pnas.2203576119


How a protein performs uphill electron transfer for reducing inert metabolites (ACS Catalysis, June '21)

Felix Neumann and Holger Dobbek used enzymatic kinetics to explore how the ATP-dependent electron transfer between the metal-APTase reductive activator of CoFeSP (RACo) and its B12-dependent partner (CoFeSP) takes place. These insights into the mechanism provide us with a blueprint for the efficient use of the energy of ATP in a coupling scheme involving conformational changes to generate a unidirectional uphill electron transfer.




Felix Neumann and Holger Dobbek (2021) ACS Catalysis, 11, 8565 DOI:10.1021/acscatal.1c01038


Untangling the sequence of events during the S2 -> S3 transition in photosystem II and implications for the water oxidation mechanism (PNASMay'20)

Mohamed Ibrahim, Rana Hussein and Holger Dobbek together with Athina Zouni (UniSysCat/SFB1078) in collaboration with colleagues from University of Heidelberg (Germany), the Lawrence Berkeley National Laboratory (CA, USA), Uppsala University (Sweden), SLAC National Accelerator Laboratory (Menlo Park, CA, USA), Umeå University (Umeå, Sweden), Diamond Light Source Ltd (UK), Rutherford Appleton Laboratory (UK), RIKEN Spring-8 Center (Hyogo, Japan), UCSF (San Francisco, CA, USA), and UC Berkeley (CA, USA) used time-resolved crystallography (XFEL) to untangle the sequence of events during the S2 -> S3 transition. 




Mohamed Ibrahim, M, Thomas Fransson, Ruchira Chatteerjee, Mun Hon Cheah et al (2020) PNAS DOI:10.1073/pnas.2000529117


Where does the H2 go? X-ray crystallography and Vibrational Spectroscopy Reveal the Key Determinants of Biocatalytic Dihydrogen Cycling by [NiFe] Hydrogenases (Angew. Chem. Int. Ed, October '19)

Yulia Ilina, Jae-Hun Jeoung and Holger Dobbek together with colleagues from the group of Ingo Zegber (Unicat, TU Berlin, Germany) used X-ray crystallography and vibrational spectroscopy to show that the protein matrix tunes the [NiFe] active site for efficient H2 binding and conversion. 




Yulia Ilina, Christian Lorent, Sagde Katz, Jae-Hun Jeoung, Seigo Shima, Marius Horch, Ingo Zebger and Holger Dobbek (2019) Ang. Int Ed Chem, 58, 18299 DOI: 10.1002/anie.201908258


A novel [Fe8S9] double-cubane cluster for ATP-dependent substrate reduction (PNAS, March '18)

Jae-Hun Jeoung and Holger Dobbek used bioinformatic tools, kinetics and X-ray crystallography to describe a novel two-component enzyme catalyzing the chemically demanding reduction of small molecules (acetylene, azide, hydrazine), reactions so far known to be the hallmark of nitrogenases.

The two components are the DCCP (double-cubane cluster protein) and its reductase, DCCP-R (R for Reductase). DCCP-R energizes electrons at the expense of ATP hydrolysis and these electrons are then used by the DCCP to reduce small molecule substrates at the active site [Fe8S9] double-cubane cluster. Although known from synthetic inorganic chemistry, this double-cubane cluster is unprecedented in biology. Comparison with members of the same ATP-dependent energizing electron systems, suggest it to be the first member of a novel enzyme family.


DCCP webpage

Jae-Hun Jeoung and Holger Dobbek (2018) PNAS, 115, 2994 DOI: 10.1073/pnas.1720489115


A catalytic active Michaelis-complex shows its secrets (Nature Communications, July '17)

Tobias Werther and Holger Dobbek together with colleagues from the group of Peter Hildebrandt (Unicat, TU Berlin, Germany) used X-ray crystallography and resonance Raman spectroscopy to investigate the Michaelis complex of xenobiotic reductase A (reactive reduced cofactor bound to its substrates) and compare it to the non-reactive oxidized Michaelis complex mimics.

Tobias Werther and colleagues found that substrates bind in different orientations to the oxidized and reduced flavin, in both cases flattening its structure. But only authentic Michaelis complexes display an unexpected rich vibrational band pattern uncovering a strong donor–acceptor complex between reduced flavin and substrate. This interaction likely activates the catalytic ground state of the reduced flavin, accelerating the reaction within a compressed cofactor–substrate complex.



Tobias Werther, Stefan Wahlefeld, Johannes Salewski, Uwe Kuhlmann, Ingo Zebger, Peter Hilderbrandt and Holger Dobbek (2017) Nature Communications, 8, 16084. DOI: 10.1038/ncomms16084


Activation of dioxygen at a side-on O2-Nickel complex (Angew. Chem. Int. Ed, February '16)

Jae-Hun Jeoung and Holger Dobbek together with colleagues from the group of Susanne Fetzner (Westfälische Wilhelms-Universität Münster, Germany) describe the catalytic role of nickel in quercetinase (QueD). QueD belongs to the cupin superfamily, which uses a conserved 3-His-1-Glu motif to bind a metal ion. Previous work from S. Fetzner's group pointed that QueD shows highest activity with nickel(2+), an unusual cofactor for oxygenases. By using a crystalographic cryotrapping approach, Jae-Hun and Co. were able to show how binding of quercetin primes Ni(2+) to bind dioxygen on a side-on modus, ready to react with quercetin.

Jae Hun Quercetin TOC ver1


Jae-Hun Jeoung. Dimitrios Nianios, Susanne Fetzner, and Holger Dobbek (2016) Angew. Chem. Int. Ed., 55, 3281. DOI: 10.1002/anie.201510741


A blue print for the activation of Carbon Dioxide (Angew. Chem. Int. Ed, July '15)

Jochen Fesseler, Jae-Hun Jeoung and Holger Dobbek describe in unprecedented details how the activation of CO2 and its isoelectronic analogue NCO is achieved at a complex biological metal center. Carbon monoxide dehydrogenase (CODH) employs a [NiFe4S4] cluster (cluster C) to bind and activate CO2, which is subsequently split into CO and water. By using x-ray crystallography, the authors were able to describe the clusters geometry with bound substrate CO2 and its inhibitor NCO under turnover conditions at true-atomic resolution (dmin < 1.1 Å).

„Our insights will be of great help for synthetic inorganic and theoretical chemists“, explains Jochen Fesseler, lead author of the study. “By using our high-resolution structures as a blue print, complexes with comparable catalytic power could be developed for large-scale CO2 conversions in the future.“

AngChem 2015


Jochen Fesseler, Jae-Hun Jeoung, and Holger Dobbek (2015) Angew. Chem. Int. Ed., 54, 8560 DOI: 10.1002/anie.201501778 (English) ; DOI: 10.1002/ange.201501778 (german)


How bacteria respires organohalide pollutants (Science, October '14)

Martin Bommer, Jochen Fesseler and Holger Dobbek together with colleagues from the group of Gabriele Diekert (Jena University, Germany) describe for the first time the crystal structure of PceA, an archetypal dehalogenase from Sulfurospirillum multivorans, a organohalide-respiring microorganism.



Martin Bommer, Cindy Kunze, Jochen Fesseler, Thorsten Schubert, Gabriele Diekert, and Holger Dobbek (2014) Science, 346, 455 DOI:10.1126/science.1258118