Stefan Knapp

Stefan Knapp

SGC Frankfurt

Knapp

Biography

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.

Research Areas

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.

2009

HD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain.

Gingras MC, Zhang YL, Kharitidi D, Barr AJ, Knapp S, Tremblay ML, Pause A

PLoS ONE. 2009-4-2 . 4(4):e5105 .doi: 10.1371/journal.pone.0005105

PMID: 19340315

Structure of dystrophia myotonica protein kinase.

Elkins JM, Amos A, Niesen FH, Pike AC, Fedorov O, Knapp S

Protein Sci.. 2009-3-25 . 18(4):782-91 .doi: 10.1002/pro.82

PMID: 19309729

Kinase domain insertions define distinct roles of CLK kinases in SR protein phosphorylation.

Bullock AN, Das S, Debreczeni JE, Rellos P, Fedorov O, Niesen FH, Guo K, Papagrigoriou E, Amos AL, Cho S, Turk BE, Ghosh G, Knapp S

Structure. 2009-3-11 . 17(3):352-62 .doi: 10.1016/j.str.2008.12.023

PMID: 19278650

Large-scale structural analysis of the classical human protein tyrosine phosphatome.

Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I, Savitsky P, Burgess-Brown NA, Müller S, Knapp S

Cell. 2009-1-23 . 136(2):352-63 .doi: 10.1016/j.cell.2008.11.038

PMID: 19167335

Targeting group II PAKs in cancer and metastasis.

Eswaran J, Soundararajan M, Knapp S

Cancer Metastasis Rev.. 2009-1-23 . 28(1-2):209-17 .doi: 10.1007/s10555-008-9181-4

PMID: 19160016

Discovery of a potent and selective inhibitor for human carbonyl reductase 1 from propionate scanning applied to the macrolide zearalenone.

Zimmermann TJ, Niesen FH, Pilka ES, Knapp S, Oppermann U, Maier ME

Bioorg. Med. Chem.. 2009-1-15 . 17(2):530-6 .doi: 10.1016/j.bmc.2008.11.076

PMID: 19097799

2008

Extremely tight binding of a ruthenium complex to glycogen synthase kinase 3.

Atilla-Gokcumen GE, Pagano N, Streu C, Maksimoska J, Filippakopoulos P, Knapp S, Meggers E

Chembiochem. 2008-12-15 . 9(18):2933-6 .doi: 10.1002/cbic.200800489

PMID: 19035373

Thermal unfolding of the archaeal DNA and RNA binding protein Ssh10.

Wu X, Oppermann M, Berndt KD, Bergman T, Jörnvall H, Knapp S, Oppermann U

Biochem. Biophys. Res. Commun.. 2008-9-5 . 373(4):482-7 .doi: 10.1016/j.bbrc.2008.06.030

PMID: 18571501

Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation.

Filippakopoulos P, Kofler M, Hantschel O, Gish GD, Grebien F, Salah E, Neudecker P, Kay LE, Turk BE, Superti-Furga G, Pawson T, Knapp S

Cell. 2008-9-5 . 134(5):793-803 .doi: 10.1016/j.cell.2008.07.047

PMID: 18775312