Molecular Recognition and Catalysis
Our mission is to understand and manipulate macromolecular machines and systems. For their understanding, we follow a holistic approach, in which we integrate a variety of structural methods with biochemical, biophysical and computational approaches. For their manipulation, we exploit our findings for drug discovery and development, often in collaboration with medicinal chemists.
Our group maintains two main lines of research. The first line focusses on basic research on the spatial organization, functional dynamics, and druggability of biomolecular interactions in metabolic pathways, molecular signaling processes and macromolecular complexes. The second line focusses on individual pharmacological targets, with a strong emphasis on targeted protein degradation via the repurposing of E3 ubiquitin ligases.
We generally rely on the integration of complementary methods to obtain insight into dynamics and to overcome technical artifacts of individual methods. For structural characterization, we routinely employ X-ray crystallography, SAXS, and - in collaboration - NMR and Cryo-EM, which we complement with computational approaches. For drug targets, we dissect the structure-activity relationship of small molecules using X-ray crystallography and develop bespoken biophysical assays.
Sweet and Blind Spots in E3 Ligase Ligand Space Revealed by a Thermophoresis-Based Assay
Maiwald S*, Heim C*, Hernandez Alvarez B, Hartmann MD. ACS Med Chem Lett (2021)
Architecture and functional dynamics of the pentafunctional AROM complex
Arora Verasztó, H, Logotheti, M, Albrecht, R, Leitner, A, Zhu, H, Hartmann, MD. Nat Chem Biol (2020)
De-Novo Design of Cereblon (CRBN) Effectors Guided by Natural Hydrolysis Products of Thalidomide Derivatives
Heim C, Pliatsika D, Mousavizadeh F, Bär K, Hernandez Alvarez B, Giannis A, Hartmann MD. J Med Chem (2019)
On the Origins of Symmetry and Modularity in the Proteasome Family
Fuchs ACD, Hartmann MD. Bioessays (2019)
Chemical Ligand Space of Cereblon
Boichenko I, Bär K, Deiss S, Heim C, Albrecht R, Lupas AN, Hernandez Alvarez B, Hartmann MD. ACS Omega (2018)
The Architecture of the Anbu Complex Reflects an Evolutionary Intermediate at the Origin of the Proteasome System
Fuchs ACD, Alva V, Maldoner L, Albrecht R, Hartmann MD, Martin J. Structure (2017)
A widespread glutamine-sensing mechanism in the plant kingdom
Chellamuthu VR, Ermilova E, Lapina T, Lüddecke J, Minaeva E, Herrmann C, Hartmann MD, Forchhammer K. Cell (2014)