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.

2007

Structural and functional characterization of the human protein kinase ASK1.

Bunkoczi G, Salah E, Filippakopoulos P, Fedorov O, Müller S, Sobott F, Parker SA, Zhang H, Min W, Turk BE, Knapp S

Structure. 2007-10-17 . 15(10):1215-26 .doi: 10.1016/j.str.2007.08.011

PMID: 17937911

The scientific impact of the Structural Genomics Consortium: a protein family and ligand-centered approach to medically-relevant human proteins.

Gileadi O, Knapp S, Lee WH, Marsden BD, Müller S, Niesen FH, Kavanagh KL, Ball LJ, von Delft F, Doyle DA, Oppermann UC, Sundström M

J. Struct. Funct. Genomics. 2007-10-12 . 8(2-3):107-19 .doi: 10.1007/s10969-007-9027-2

PMID: 17932789

Structural analysis identifies imidazo[1,2-b]pyridazines as PIM kinase inhibitors with in vitro antileukemic activity.

Pogacic V, Bullock AN, Fedorov O, Filippakopoulos P, Gasser C, Biondi A, Meyer-Monard S, Knapp S, Schwaller J

Cancer Res.. 2007-7-15 . 67(14):6916-24 .doi: 10.1158/0008-5472.CAN-07-0320

PMID: 17638903

Activation segment exchange: a common mechanism of kinase autophosphorylation?

Oliver AW, Knapp S, Pearl LH

Trends Biochem. Sci.. 2007-7-12 . 32(8):351-6 .doi: 10.1016/j.tibs.2007.06.004

PMID: 17627826

Specificity profiling of Pak kinases allows identification of novel phosphorylation sites.

Rennefahrt UE, Deacon SW, Parker SA, Devarajan K, Beeser A, Chernoff J, Knapp S, Turk BE, Peterson JR

J. Biol. Chem.. 2007-5-25 . 282(21):15667-78 .doi: 10.1074/jbc.M700253200

PMID: 17392278

Structures of the human eIF4E homologous protein, h4EHP, in its m7GTP-bound and unliganded forms.

Rosettani P, Knapp S, Vismara MG, Rusconi L, Cameron AD

J. Mol. Biol.. 2007-5-4 . 368(3):691-705 .doi: 10.1016/j.jmb.2007.02.019

PMID: 17368478

Protein-protein interaction site mapping using NMR-detected mutational scanning.

Baminger B, Ludwiczek ML, Kontaxis G, Knapp S, Konrat R

J. Biomol. NMR. 2007-4-20 . 38(2):133-7 .doi: 10.1007/s10858-007-9154-x

PMID: 17447011

Insights for the development of specific kinase inhibitors by targeted structural genomics.

Fedorov O, Sundström M, Marsden B, Knapp S

Drug Discov. Today. 2007-3-29 . 12(9-10):365-72 .doi: 10.1016/j.drudis.2007.03.006

PMID: 17467572

Structure and regulation of the human Nek2 centrosomal kinase.

Rellos P, Ivins FJ, Baxter JE, Pike A, Nott TJ, Parkinson DM, Das S, Howell S, Fedorov O, Shen QY, Fry AM, Knapp S, Smerdon SJ

J. Biol. Chem.. 2007-3-2 . 282(9):6833-42 .doi: 10.1074/jbc.M609721200

PMID: 17197699

Biochemical characterization of TASSELSEED 2, an essential plant short-chain dehydrogenase/reductase with broad spectrum activities.

Wu X, Knapp S, Stamp A, Stammers DK, Jörnvall H, Dellaporta SL, Oppermann U

FEBS J.. 2007-2-15 . 274(5):1172-82 .doi: 10.1111/j.1742-4658.2007.05642.x

PMID: 17298439