Prof Stefan Knapp studied Chemistry at the University of Marburg (Germany) and at the University of Illinois (USA). He did his PhD in protein crystallography at the Karolinska Institute in Stockholm (Sweden) (1996) and continued his career at the Karolinska Institute as a postdoctoral scientist (1996-1999). In 1999, he joined the Pharmacia Corporation as a principal research scientist in structural biology and biophysics. He left the company in 2004 to set up a research group at the Structural Genomics Consortium at Oxford University (SGC). From 2008 to 2015 he was a Professor of Structural Biology at the Nuffield Department of Clinical Medicine (NDM) at Oxford University (UK) and between 2012 and 2015 he was the Director for Chemical Biology at the Target Discovery Institute (TDI). He joined Frankfurt University (Germany) in 2015 as a Professor of Pharmaceutical Chemistry and the Buchmann Institute of Molecular Life Sciences. He remains associated to the SGC as a visiting Professor at Oxford and he is also adjunct Professor of the George Washington University. Since 2017 he is the CSO of the newly founded SGC node at the Goethe-University Frankfurt. His research interests are the rational design of selective inhibitors that target protein kinases as well as protein interactions modules that function as reader domains of the epigenetic code.
My laboratory is interested in understanding molecular mechanisms that regulate protein function of key signalling molecules and how these mechanisms can be utilized for the development of highly selective and potent inhibitors (chemical probes). As a basis for this work we have generated a comprehensive set of high resolution crystal structures that cover most members of the protein family of interest. We are particularly interested in protein interactions module of the bromodomain family that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. This effort generated several highly selective chemical probes targeting bromodomains. A second research focus is on protein kinases. Our laboratory has solved a comprehensive set of crystal structure of this large protein family offering the opportunity to understand molecular mechanisms of their regulation and developing new strategies for their selective targeting. We developed for example a number of highly selective inhibitors by exploring unusual binding modes and allosteric binding sites. A particular focus of the laboratory is also to understand structural mechanisms leading to slow binding kinetics as part of the K4DD consortium.
Schwalm MP, Dopfer J, Kumar A, Greco FA, Bauer N, Löhr F, Heering J, Cano-Franco S, Lechner S, Hanke T, Jaser I, Morasch V, Lenz C, Fearon D, Marples PG, Tomlinson CWE, Brunello L, Saxena K, Adams NBP, von Delft F, Müller S, Stolz A, Proschak E, Kuster B, Knapp S, Rogov VV
Nat Commun. 2024-11-26 . 15(1):10204 .doi: 10.1038/s41467-024-54409-5
PMID: 39587067Teichmann T, Pflüger-Müller B, Giménez VMM, Sailer F, Dirks H, Zehr S, Warwick T, Brettner F, Munoz-Tello P, Zimmer A, Tegeder I, Thomas D, Gurke R, Günther S, Heering J, Proschak E, Geisslinger G, Bibli IS, Heringdorf DMZ, Manucha W, Windbergs M, Knapp S, Weigert A, Leisegang MS, Kojetin D, Brandes RP
Br J Pharmacol. 2024-11-20 . .doi: 10.1111/bph.17366
PMID: 39563075Zhu WF, Franz HM, Krämer A, Duman E, Empel C, Göbel MW, Koenigs RM, Knapp S, Hiesinger K, Proschak E, Hernandez-Olmos V
J Org Chem. 2024-10-23 . .doi: 10.1021/acs.joc.4c01622
PMID: 39438325Molitor M, Menge A, Mandel S, George S, Müller S, Knapp S, Hofmann B, Steinhilber D, Häfner AK
Pflugers Arch. 2024-9-30 . .doi: 10.1007/s00424-024-03019-7
PMID: 39347835Krämer A, Knapp S
Signal Transduct Target Ther. 2024-9-6 . 9(1):224 .doi: 10.1038/s41392-024-01935-9
PMID: 39237495Pieper NM, Schnell J, Bruecher D, Knapp S, Vogler M
Cell Commun Signal. 2024-8-27 . 22(1):415 .doi: 10.1186/s12964-024-01782-9
PMID: 39192247Schwalm MP, Dopfer J, Knapp S, Rogov VV
Methods Mol Biol. 2024-8-8 . 2845:203-218 .doi: 10.1007/978-1-0716-4067-8_17
PMID: 39115669Dopfer J, Schwalm MP, Knapp S, Rogov VV
Methods Mol Biol. 2024-8-8 . 2845:219-235 .doi: 10.1007/978-1-0716-4067-8_18
PMID: 39115670Gerninghaus J, Zhubi R, Krämer A, Karim M, Tran DHN, Joerger AC, Schreiber C, Berger LM, Berger BT, Ehret TAL, Elson L, Lenz C, Saxena K, Müller S, Einav S, Knapp S, Hanke T
J Med Chem. 2024-7-19 . .doi: 10.1021/acs.jmedchem.4c00411
PMID: 39028937Němec V, Remeš M, Beňovský P, Böck MC, Šranková E, Wong JF, Cros J, Williams E, Tse LH, Smil D, Ensan D, Isaac MB, Al-Awar R, Gomolková R, Ursachi VC, Fafílek B, Kahounová Z, Víchová R, Vacek O, Berger BT, Wells CI, Corona CR, Vasta JD, Robers MB, Krejci P, Souček K, Bullock AN, Knapp S, Paruch K
J Med Chem. 2024-7-18 . .doi: 10.1021/acs.jmedchem.4c00629
PMID: 39023313