Molecular Recognition and Catalysis

Project Leader:   Marcus Hartmann
Department:   Protein Evolution - Lupas
Assistant:    Karin Lehmann
Phone:   +49 7071 601-340
Fax:   +49 7071 601-349
Staff:   Alphabetical List | Alumni


The function of biomolecules critically depends on specific interactions with other molecules. Therefore, molecular recognition is pivotal in biomolecular evolution and governs all biochemical processes, from ligand-binding to the assembly of macromolecular complexes.

We study biomolecular interactions in different contexts, employing classical biochemistry, X-ray crystallography, and spectroscopic approaches. On one end, we are interested in substrate recognition and biocatalysis. We probe the substrate spectrum and dissect the molecular mechanism of enzymes, with a focus on proteins of yet unknown function and on potential drug targets. On the other end, we are investigating regulatory protein-protein interactions in two different lines of research. In one, we are using natural bifunctional fusion enzymes to investigate how the individual proteins of metabolic pathways are potentially organized for efficient substrate funneling or feedback regulation via allosteric effects. In the other, we aim to probe the druggability of protein-protein interfaces in macromolecular complexes implicated in human disease.

Selected Publications

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)

see full publication list here

Open Positions

If you are interested in joining our team, please send a cover letter and your curriculum vitae to marcus.hartmann(at)

See also the Hartmann Lab page in the Tübingen International PhD Program for the Biological Sciences