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.
Rouka E, Simister PC, Janning M, Kumbrink J, Konstantinou T, Muniz JR, Joshi D, O'Reilly N, Volkmer R, Ritter B, Knapp S, von Delft F, Kirsch KH, Feller SM
J. Biol. Chem.. 2015-8-20 . .doi: 10.1074/jbc.M115.637207
PMID: 26296892Hammitzsch A, Tallant C, Fedorov O, O'Mahony A, Brennan PE, Hay DA, Martinez FO, Al-Mossawi MH, de Wit J, Vecellio M, Wells C, Wordsworth P, Müller S, Knapp S, Bowness P
Proc. Natl. Acad. Sci. U.S.A.. 2015-8-10 . .doi: 10.1073/pnas.1501956112
PMID: 26261308Chaikuad A, Knapp S, von Delft F
Acta Crystallogr. D Biol. Crystallogr.. 2015-8-1 . 71(Pt 8):1627-39 .doi: 10.1107/S1399004715007968
PMID: 26249344Gato-Cañas M, Martinez de Morentin X, Blanco-Luquin I, Fernandez-Irigoyen J, Zudaire I, Liechtenstein T, Arasanz H, Lozano T, Casares N, Chaikuad A, Knapp S, Guerrero-Setas D, Escors D, Kochan G, Santamaría E
Oncotarget. 2015-7-23 .
PMID: 26320174Huston A, Arrowsmith CH, Knapp S, Schapira M
Nat. Chem. Biol.. 2015-7-21 . 11(8):542-5 .doi: 10.1038/nchembio.1871
PMID: 26196765Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, Bountra C, Brennan PE, Brown PJ, Bunnage ME, Buser-Doepner C, Campbell RM, Carter AJ, Cohen P, Copeland RA, Cravatt B, Dahlin JL, Dhanak D, Edwards AM, Frye SV, Gray N, Grimshaw CE, Hepworth D, Howe T, Huber KV, Jin J, Knapp S, Kotz JD, Kruger RG, Lowe D, Mader MM, Marsden B, Mueller-Fahrnow A, Müller S, O'Hagan RC, Overington JP, Owen DR, Rosenberg SH, Roth B, Ross R, Schapira M, Schreiber SL, Shoichet B, Sundström M, Superti-Furga G, Taunton J, Toledo-Sherman L, Walpole C, Walters MA, Willson TM, Workman P, Young RN, Zuercher WJ
Nat. Chem. Biol.. 2015-7-21 . 11(8):536-41 .doi: 10.1038/nchembio.1867
PMID: 26196764Alexander LT, Moebitz H, Drueckes P, Savitsky P, Fedorov O, Elkins JM, Deane CM, Cowan-Jacob SW, Knapp S
ACS Chem. Biol.. 2015-7-9 . .doi: 10.1021/acschembio.5b00398
PMID: 26158339Harrington L, Alexander LT, Knapp S, Bayley H
Angew. Chem. Int. Ed. Engl.. 2015-6-8 . .doi: 10.1002/anie.201503141
PMID: 26058458Clark PG, Vieira LC, Tallant C, Fedorov O, Singleton DC, Rogers CM, Monteiro OP, Bennett JM, Baronio R, Müller S, Daniels DL, Méndez J, Knapp S, Brennan PE, Dixon DJ
Angew Chem Weinheim Bergstr Ger. 2015-5-18 . 127(21):6315-6319 .doi: 10.1002/ange.201501394
PMID: 27346896Bennett JM, Fedorov O, Tallant C, Monteiro OP, Meier J, Gamble V, Savitski P, Nunez-Alonso GA, Haendler B, Rogers C, Brennan PE, Müller S, Knapp S
J. Med. Chem.. 2015-5-14 . .doi: 10.1021/acs.jmedchem.5b00458
PMID: 25974391