|Project Leader:||Marcus Hartmann|
|Department:||Protein Evolution - Lupas|
|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.
Arora Verasztó, H., Logotheti, M., Albrecht, R., Leitner, A., Zhu, H., Hartmann, MD. (2020). Architecture and functional dynamics of the pentafunctional AROM complex. Nat Chem Biol. 10.
Heim C, Pliatsika D, Mousavizadeh F, Bär K, Hernandez Alvarez B, Giannis A, Hartmann MD. (2019). De-Novo Design of Cereblon (CRBN) Effectors Guided by Natural Hydrolysis Products of Thalidomide Derivatives. J Med Chem. 62, 6615-6629.
Fuchs ACD, Hartmann MD. (2019). On the Origins of Symmetry and Modularity in the Proteasome Family: Symmetry Transitions are Pivotal in the Evolution and Functional Diversification of Self-Compartmentalizing Proteases. Bioessays. 41 e1800237.
Boichenko I, Bär K, Deiss S, Heim C, Albrecht R, Lupas AN, Hernandez Alvarez B, Hartmann MD. (2018). Chemical Ligand Space of Cereblon. ACS Omega. 9, 11163-11171.
Fuchs ACD, Alva V, Maldoner L, Albrecht R, Hartmann MD, Martin J. (2017). The Architecture of the Anbu Complex Reflects an Evolutionary Intermediate at the Origin of the Proteasome System. Structure. 25, 834-845.
Hartmann MD. (2017). Functional and Structural Roles of Coiled Coils. Subcell Biochem. 2017 82, 63-93.
Chellamuthu VR, Ermilova E, Lapina T, Lüddecke J, Minaeva E, Herrmann C, Hartmann MD, Forchhammer K. (2014). A widespread glutamine-sensing mechanism in the plant kingdom. Cell. 159, 1188-1199.