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.
Mathea S, Salah E, Tallant C, Chatterjee D, Berger BT, Konietzny R, Müller-Knapp S, Kessler BM, Knapp S
Biochem J. 2021-6-30 . .doi: 10.1042/BCJ20210257
PMID: 34190988Faudone G, Bischoff-Kont I, Rachor L, Willems S, Zhubi R, Kaiser A, Chaikuad A, Knapp S, Fürst R, Heering J, Merk D
J Med Chem. 2021-6-11 . .doi: 10.1021/acs.jmedchem.1c00733
PMID: 34115934Schmidt SH, Weng JH, Aoto PC, Boassa D, Mathea S, Silletti S, Hu J, Wallbott M, Komives EA, Knapp S, Herberg FW, Taylor SS
Proc Natl Acad Sci U S A. 2021-6-8 . 118(23): .doi: 10.1073/pnas.2100844118
PMID: 34088839Tesch R, Rak M, Raab M, Berger LM, Kronenberger T, Joerger AC, Berger BT, Abdi I, Hanke T, Poso A, Strebhardt K, Sanhaji M, Knapp S
J Med Chem. 2021-6-4 . .doi: 10.1021/acs.jmedchem.0c02144
PMID: 34086472Reynders M, Chaikuad A, Berger BT, Bauer K, Koch P, Laufer S, Knapp S, Trauner D
Angew Chem Int Ed Engl. 2021-6-3 . .doi: 10.1002/anie.202103767
PMID: 34081840Amrhein JA, Knapp S, Hanke T
J Med Chem. 2021-6-2 . .doi: 10.1021/acs.jmedchem.1c00217
PMID: 34076436Krishnathas GM, Strödke B, Mittmann L, Zech T, Berger LM, Reichel CA, Rösser S, Schmid T, Knapp S, Müller S, Bracher F, Fürst R, Bischoff-Kont I
FASEB J. 2021-5-28 . 35(6):e21656 .doi: 10.1096/fj.202100037R
PMID: 34042211Altincekic N, Korn SM, Qureshi NS, Dujardin M, Ninot-Pedrosa M, Abele R, Abi Saad MJ, Alfano C, Almeida FCL, Alshamleh I, de Amorim GC, Anderson TK, Anobom CD, Anorma C, Bains JK, Bax A, Blackledge M, Blechar J, Böckmann A, Brigandat L, Bula A, Bütikofer M, Camacho-Zarco AR, Carlomagno T, Caruso IP, Ceylan B, Chaikuad A, Chu F, Cole L, Crosby MG, de Jesus V, Dhamotharan K, Felli IC, Ferner J, Fleischmann Y, Fogeron ML, Fourkiotis NK, Fuks C, Fürtig B, Gallo A, Gande SL, Gerez JA, Ghosh D, Gomes-Neto F, Gorbatyuk O, Guseva S, Hacker C, Häfner S, Hao B, Hargittay B, Henzler-Wildman K, Hoch JC, Hohmann KF, Hutchison MT, Jaudzems K, Jović K, Kaderli J, Kalniņš G, Kaņepe I, Kirchdoerfer RN, Kirkpatrick J, Knapp S, Krishnathas R, Kutz F, Zur Lage S, Lambertz R, Lang A, Laurents D, Lecoq L, Linhard V, Löhr F, Malki A, Bessa LM, Martin RW, Matzel T, Maurin D, McNutt SW, Mebus-Antunes NC, Meier BH, Meiser N, Mompeán M, Monaca E, Montserret R, Mariño Perez L, Moser C, Muhle-Goll C, Neves-Martins TC, Ni X, Norton-Baker B, Pierattelli R, Pontoriero L, Pustovalova Y, Ohlenschläger O, Orts J, Da Poian AT, Pyper DJ, Richter C, Riek R, Rienstra CM, Robertson A, Pinheiro AS, Sabbatella R, Salvi N, Saxena K, Schulte L, Schiavina M, Schwalbe H, Silber M, Almeida MDS, Sprague-Piercy MA, Spyroulias GA, Sreeramulu S, Tants JN, Tārs K, Torres F, Töws S, Treviño MÁ, Trucks S, Tsika AC, Varga K, Wang Y, Weber ME, Weigand JE, Wiedemann C, Wirmer-Bartoschek J, Wirtz Martin MA, Zehnder J, Hengesbach M, Schlundt A
Front Mol Biosci. 2021-5-28 . 8:653148 .doi: 10.3389/fmolb.2021.653148
PMID: 34041264Dölle A, Adhikari B, Krämer A, Weckesser J, Berner N, Berger LM, Diebold M, Szewczyk MM, Barsyte-Lovejoy D, Arrowsmith CH, Gebel J, Löhr F, Dötsch V, Eilers M, Heinzlmeir S, Kuster B, Sotriffer C, Wolf E, Knapp S
J Med Chem. 2021-5-13 . .doi: 10.1021/acs.jmedchem.1c00146
PMID: 33980013Willems S, Gellrich L, Chaikuad A, Kluge S, Werz O, Heering J, Knapp S, Lorkowski S, Schubert-Zsilavecz M, Merk D
Cell Chem Biol. 2021-5-12 . .doi: 10.1016/j.chembiol.2021.04.019
PMID: 33989565