Jon Elkins

Group Leader - Kinases

University of Oxford
Group: 
Kinases
+44(0) 1865-617751

Jon did a DPhil in chemistry in the lab of Professor Sir Jack Baldwin at the University of Oxford, working on antibiotic biosynthesis and 2-oxoglutarate-dependent dioxygenases. He did a post-doc in the lab of Professor Chris Schofield working on the Hypoxia-inducible-factor hydroxylase Factor-Inhibiting-HIF and enzymes involved in biosynthesis of clavulanic acid. He joined the SGC in 2004 with responsibility for a team producing structures of proteins involved in membrane receptor signalling such as GTPases, 14-3-3 proteins, RGS domains and PDZ domains. Since 2007 he has focussed his research on kinase structural biology and structures of key proteins involved in cell signalling.

Research Areas

We are interested in understanding the molecular mechanisms of proteins involved in cellular signalling, especially those involved in phosphorylation such as protein kinases. There are over 500 protein kinases in the human genome and most of them remain poorly characterized despite the importance of signalling in regulating physiology. Our approach is to use high resolution structural information for the generation of selective inhibitors (chemical probes) which we use to gain understanding of the functions of these largely uncharacterized proteins. Our lab generated a large repository of efficient expression systems, recombinant proteins and crystal structures that now enables family wide structural comparison and screening. Together with the recently established SGC site at the University of Campinas we aim to generate new chemical probes against novel protein kinases. We also have research interests in cellular regulation by ADP-ribosylation, which links epigenetics to metabolism; lipid kinases; and sphingolipid biosynthesis, which has strong links to both inflammation and cancer, and where mutations in the various proteins involved are associated with a variety of rare diseases.

Group Members

  • Jing Wang
  • Kamal Abdul Azeez
  • Eidarus Salah
  • Clara Redondo
  • Fiona Sorrell
  • Marion Schuller

Publications

Family-wide Structural Analysis of Human Numb-Associated Protein Kinases.
Sorrell, FJ; Szklarz, M; Abdul Azeez, KR; Elkins, JM; Knapp, S;
Structure. 2016 24:401-411. doi:
PMID: 26853940

Comprehensive characterization of the Published Kinase Inhibitor Set.
Elkins, JM; Fedele, V; Szklarz, M; Abdul Azeez, KR; Salah, E; Mikolajczyk, J; Romanov, S; Sepetov, N; Huang, XP; Roth, BL; Al Haj Zen, A; Fourches, D; Muratov, E; Tropsha, A; Morris, J; Teicher, BA; Kunkel, M; Polley, E; Lackey, KE; Atkinson, FL; Overington, JP; Bamborough, P; Müller, S; Price, DJ; Willson, TM; Drewry, DH; Knapp, S; Zuercher, WJ;
Nature Biotechnology. 2016 34:95-103. doi:
PMID: 26501955

Crystal Structure of Sphingosine Kinase 1 with PF-543.
Wang, J; Knapp, S; Pyne, NJ; Pyne, S; Elkins, JM;
ACS Medicinal Chemistry Letters. 2014 5:1329-1333. doi:
PMID: 25516793

The crystal structure of the RhoA-AKAP-Lbc DH-PH domain complex.
Abdul Azeez, KR; Knapp, S; Fernandes, JM; Klussmann, E; Elkins, JM;
Biochemical Journal. 2014 464:231-239. doi:
PMID: 25186459

Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy.
Huber, KV; Salah, E; Radic, B; Gridling, M; Elkins, JM; Stukalov, A; Jemth, AS; Göktürk, C; Sanjiv, K; Strömberg, K; Pham, T; Berglund, UW; Colinge, J; Bennett, KL; Loizou, JI; Helleday, T; Knapp, S; Superti-Furga, G;
Nature. 2014 508:222-227. doi:
PMID: 24695225

Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition.
Soundararajan, M; Roos, AK; Savitsky, P; Filippakopoulos, P; Kettenbach, AN; Olsen, JV; Gerber, SA; Eswaran, J; Knapp, S; Elkins, JM;
Structure. 2013 21:986-996. doi: 10.1016/j.str.2013.03.012
PMID: 23665168

X-ray crystal structure of ERK5 (MAPK7) in complex with a specific inhibitor.
Elkins, JM; Wang, J; Deng, X; Pattison, MJ; Arthur, JS; Erazo, T; Gomez, N; Lizcano, JM; Gray, NS; Knapp, S;
Journal of Medicinal Chemistry. 2013 56:4413-4421. doi: 10.1021/jm4000837
PMID: 23656407

Structural insights into the activation of MST3 by MO25
Mehellou, Y; Alessi, DR; Macartney, TJ; Szklarz, M; Knapp, S; Elkins, JM;
Biochemical and Biophysical Research Communications. 2013 :-. doi:
PMID: 23296203

Crystal structure of human aurora B in complex with INCENP and VX-680.
Elkins, JM; Santaguida, S; Musacchio, A; Knapp, S;
Journal of Medicinal Chemistry. 2012 55:7841-7848. doi: 10.1021/jm3008954
PMID: 22920039

Structural basis for protein-protein interactions in the 14-3-3 protein family.
Yang, X; Lee, WH; Sobott, F; Papagrigoriou, E; Robinson, CV; Grossmann, JG; Sundström, M; Doyle, DA; Elkins, JM;
Proceedings of the National Academy of Sciences of USA. 2006 103:17237-17242. doi: 10.1073/pnas.0605779103
PMID: 17085597

Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha.
Elkins, JM; Hewitson, KS; McNeill, LA; Seibel, JF; Schlemminger, I; Pugh, CW; Ratcliffe, PJ; Schofield, CJ;
Journal of Biological Chemistry. 2003 278:1802-1806. doi: 10.1074/jbc.C200644200
PMID: 12446723

2016

Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors.
Zhang, T; Kwiatkowski, N; Olson, CM; Dixon-Clarke, SE; Abraham, BJ; Greifenberg, AK; Ficarro, SB; Elkins, JM; Liang, Y; Hannett, NM; Manz, T; Hao, M; Bartkowiak, B; Greenleaf, AL; Marto, JA; Geyer, M; Bullock, AN; Young, RA; Gray, NS;
Nature Chemical Biology. 2016 12:876-884. doi:
PMID: 27571479

Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche.
Miranda, F; Mannion, D; Liu, S; Zheng, Y; Mangala, LS; Redondo, C; Herrero-Gonzalez, S; Xu, R; Taylor, C; Chedom, DF; Karaminejadranjbar, M; Albukhari, A; Jiang, D; Pradeep, S; Rodriguez-Aguayo, C; Lopez-Berestein, G; Salah, E; Abdul Azeez, KR; Elkins, JM; Campo, L; Myers, KA; Klotz, D; Bivona, S; Dhar, S; Bast, RC; Saya, H; Choi, HG; Gray, NS; Fischer, R; Kessler, BM; Yau, C; Sood, AK; Motohara, T; Knapp, S; Ahmed, AA;
Cancer Cell. 2016 30:273-289. doi:
PMID: 27478041

Family-wide Structural Analysis of Human Numb-Associated Protein Kinases.
Sorrell, FJ; Szklarz, M; Abdul Azeez, KR; Elkins, JM; Knapp, S;
Structure. 2016 24:401-411. doi:
PMID: 26853940

The Intersection of Structural and Chemical Biology - An Essential Synergy.
Zuercher, WJ; Elkins, JM; Knapp, S;
Cell chemical biology. 2016 23:173-182. doi:
PMID: 26933743

Comprehensive characterization of the Published Kinase Inhibitor Set.
Elkins, JM; Fedele, V; Szklarz, M; Abdul Azeez, KR; Salah, E; Mikolajczyk, J; Romanov, S; Sepetov, N; Huang, XP; Roth, BL; Al Haj Zen, A; Fourches, D; Muratov, E; Tropsha, A; Morris, J; Teicher, BA; Kunkel, M; Polley, E; Lackey, KE; Atkinson, FL; Overington, JP; Bamborough, P; Müller, S; Price, DJ; Willson, TM; Drewry, DH; Knapp, S; Zuercher, WJ;
Nature Biotechnology. 2016 34:95-103. doi:
PMID: 26501955

2015

Structures of the CDK12/CycK complex with AMP-PNP reveal a flexible C-terminal kinase extension important for ATP binding.
Dixon-Clarke, SE; Elkins, JM; Cheng, SW; Morin, GB; Bullock, AN;
Scientific Reports. 2015 5:17122-. doi:
PMID: 26597175

Type II Inhibitors Targeting CDK2.
Alexander, LT; Möbitz, H; Drueckes, P; Savitsky, P; Fedorov, O; Elkins, JM; Deane, CM; Cowan-Jacob, SW; Knapp, S;
ACS Chemical Biology. 2015 10:2116-2125. doi:
PMID: 26158339

Identification and structure-function analysis of subfamily selective G protein-coupled receptor kinase inhibitors.
Homan, KT; Larimore, KM; Elkins, JM; Szklarz, M; Knapp, S; Tesmer, JJ;
ACS Chemical Biology. 2015 10:310-319. doi:
PMID: 25238254

2014

Crystal Structure of Sphingosine Kinase 1 with PF-543.
Wang, J; Knapp, S; Pyne, NJ; Pyne, S; Elkins, JM;
ACS Medicinal Chemistry Letters. 2014 5:1329-1333. doi:
PMID: 25516793

The crystal structure of the RhoA-AKAP-Lbc DH-PH domain complex.
Abdul Azeez, KR; Knapp, S; Fernandes, JM; Klussmann, E; Elkins, JM;
Biochemical Journal. 2014 464:231-239. doi:
PMID: 25186459

Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy.
Huber, KV; Salah, E; Radic, B; Gridling, M; Elkins, JM; Stukalov, A; Jemth, AS; Göktürk, C; Sanjiv, K; Strömberg, K; Pham, T; Berglund, UW; Colinge, J; Bennett, KL; Loizou, JI; Helleday, T; Knapp, S; Superti-Furga, G;
Nature. 2014 508:222-227. doi:
PMID: 24695225

Case study--structural genomics and human protein kinases.
E, J; l, M; k, ; i, ; n, ; s, ;
Methods in Molecular Biology. 2014 1140:325-336. doi: 10.1007/978-1-4939-0354-2_24
PMID: 24590728

2013

Structural determinants for ERK5 (MAPK7) and leucine rich repeat kinase 2 activities of benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-ones
Deng, X; Elkins, JM; Zhang, J; Yang, Q; Erazo, T; Gomez, N; Choi, HG; Wang, J; Dzamko, N; Lee, JD; Sim, T; Kim, N; Alessi, DR; Lizcano, JM; Knapp, S; Gray, NS;
European Journal of Medicinal Chemistry. 2013 70:758-767. doi: 10.1016/j.ejmech.2013.10.052
PMID: 24239623

Highly functionalized terpyridines as competitive inhibitors of AKAP-PKA interactions
Schäfer, G; Milic̈, J; Eldahshan, A; Götz, F; Zühlke, K; Schillinger, C; Kreuchwig, A; Elkins, JM; Abdulazeez, KR; Oder, A; Moutty, MC; Masada, N; Beerbaum, M; Schlegel, B; Niquet, S; Schmieder, P; Krause, G; Vonkries, JP; Cooper, DMF; Knapp, S; Rademann, J; Rosenthal, W; Klussmann, E;
Angewandte Chemie International Edition. 2013 52:12187-12191. doi: 10.1002/anie.201304686
PMID: 24115519

X-ray crystal structure of ERK5 (MAPK7) in complex with a specific inhibitor.
Elkins, JM; Wang, J; Deng, X; Pattison, MJ; Arthur, JS; Erazo, T; Gomez, N; Lizcano, JM; Gray, NS; Knapp, S;
Journal of Medicinal Chemistry. 2013 56:4413-4421. doi: 10.1021/jm4000837
PMID: 23656407

Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition.
Soundararajan, M; Roos, AK; Savitsky, P; Filippakopoulos, P; Kettenbach, AN; Olsen, JV; Gerber, SA; Eswaran, J; Knapp, S; Elkins, JM;
Structure. 2013 21:986-996. doi: 10.1016/j.str.2013.03.012
PMID: 23665168

Structural insights into the activation of MST3 by MO25
Mehellou, Y; Alessi, DR; Macartney, TJ; Szklarz, M; Knapp, S; Elkins, JM;
Biochemical and Biophysical Research Communications. 2013 :-. doi:
PMID: 23296203

2012

Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B.
Tahtouh, T; Elkins, JM; Filippakopoulos, P; Soundararajan, M; Burgy, G; Durieu, E; Cochet, C; Schmid, RS; Lo, DC; Delhommel, F; Oberholzer, AE; Pearl, LH; Carreaux, F; Bazureau, JP; Knapp, S; Meijer, L;
Journal of Medicinal Chemistry. 2012 55:9312-9330. doi: 10.1021/jm301034u
PMID: 22998443

Crystal structure of human aurora B in complex with INCENP and VX-680.
Elkins, JM; Santaguida, S; Musacchio, A; Knapp, S;
Journal of Medicinal Chemistry. 2012 55:7841-7848. doi: 10.1021/jm3008954
PMID: 22920039

Fragment screening of cyclin G-associated kinase by weak affinity chromatography
Meiby, E; Knapp, S; Elkins, JM; Ohlson, S;
Analytical and Bioanalytical Chemistry. 2012 :1-9. doi:
PMID: 22918538

Analysis of conditions affecting auto-phosphorylation of human kinases during expression in bacteria.
Shrestha, A; Hamilton, G; O'Neill, E; Knapp, S; Elkins, JM;
Protein Expression and Purification. 2012 81:136-143. doi: 10.1016/j.pep.2011.09.012
PMID: 21985771

2011

Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class.
Salah, E; Ugochukwu, E; Barr, AJ; von Delft, F; Knapp, S; Elkins, JM;
Journal of Medicinal Chemistry. 2011 54:2359-2367. doi: 10.1021/jm101506n
PMID: 21417343

2010

Unusual binding interactions in PDZ domain crystal structures help explain binding mechanisms.
Elkins, JM; Gileadi, C; Shrestha, L; Phillips, C; Wang, J; Muniz, JR; Doyle, DA;
Protein Science. 2010 19:731-741. doi: 10.1002/pro.349
PMID: 20120020

2009

Structure of dystrophia myotonica protein kinase.
Elkins, JM; Amos, A; Niesen, FH; Pike, AC; Fedorov, O; Knapp, S;
Protein Science. 2009 18:782-791. doi: 10.1002/pro.82
PMID: 19309729

2007

Backbone and sidechain 1H, 13C and 15N resonance assignments of the RGS domain from human RGS14
Dowler, EF; Diehl, A; Schmieder, P; Brockmann, C; Elkins, J; Soundararajan, M; Oschkinat, H; Ball, LJ;
Biomolecular NMR Assignments. 2007 1:95-97. doi: 10.1007/s12104-007-9029-9
PMID:

Interactions of isopenicillin N synthase with cyclopropyl-containing substrate analogues reveal new mechanistic insight.
Howard-Jones, AR; Elkins, JM; Clifton, IJ; Roach, PL; Adlington, RM; Baldwin, JE; Rutledge, PJ;
Biochemistry. 2007 46:4755-4762. doi: 10.1021/bi062314q
PMID: 17397141

Structure of PICK1 and other PDZ domains obtained with the help of self-binding C-terminal extensions.
Elkins, JM; Papagrigoriou, E; Berridge, G; Yang, X; Phillips, C; Gileadi, C; Savitsky, P; Doyle, DA;
Protein Science. 2007 16:683-694. doi:
PMID: 17384233

The centaurin gamma-1 GTPase-like domain functions as an NTPase.
Soundararajan, M; Yang, X; Elkins, JM; Sobott, F; Doyle, DA;
Biochemical Journal. 2007 401:679-688. doi: 10.1042/BJ20060555
PMID: 17037982

Resonance assignment of the RGS domain of human RGS10.
Fedorov, OY; Higman, VA; Schmieder, P; Leidert, M; Diehl, A; Elkins, J; Soundararajan, M; Oschkinat, H; Ball, LJ;
Journal of Biomolecular NMR. 2007 38:191-. doi:
PMID: 17180548

2006

NMR assignment of human RGS18
Higman, VA; Leidert, M; Diehl, A; Elkins, J; Soundararajan, M; Oschkinat, H; Ball, LJ;
Journal of Biomolecular NMR. 2006 36:72-72. doi: 10.1007/s10858-006-9061-6
PMID:

Structural basis for protein-protein interactions in the 14-3-3 protein family.
Yang, X; Lee, WH; Sobott, F; Papagrigoriou, E; Robinson, CV; Grossmann, JG; Sundström, M; Doyle, DA; Elkins, JM;
Proceedings of the National Academy of Sciences of USA. 2006 103:17237-17242. doi: 10.1073/pnas.0605779103
PMID: 17085597

2005

X-ray crystal structure of ornithine acetyltransferase from the clavulanic acid biosynthesis gene cluster.
Elkins, JM; Kershaw, NJ; Schofield, CJ;
Biochemical Journal. 2005 385:565-573. doi: 10.1042/BJ20040814
PMID: 15352873

2004

Crystal structure and mechanistic implications of N2-(2-carboxyethyl)arginine synthase, the first enzyme in the clavulanic acid biosynthesis pathway.
Caines, ME; Elkins, JM; Hewitson, KS; Schofield, CJ;
Journal of Biological Chemistry. 2004 279:5685-5692. doi: 10.1074/jbc.M310803200
PMID: 14623876

2003

The role of iron and 2-oxoglutarate oxygenases in signalling.
Hewitson, KS; McNeill, LA; Elkins, JM; Schofield, CJ;
Biochemical Society Transactions. 2003 31:510-515. doi:
PMID: 12773146

Crystallographic studies on the reaction of isopenicillin N synthase with an unsaturated substrate analogue.
Elkins, JM; Rutledge, PJ; Burzlaff, NI; Clifton, IJ; Adlington, RM; Roach, PL; Baldwin, JE;
Organic and Biomolecular Chemistry. 2003 1:1455-1460. doi:
PMID: 12926272

Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha.
Elkins, JM; Hewitson, KS; McNeill, LA; Seibel, JF; Schlemminger, I; Pugh, CW; Ratcliffe, PJ; Schofield, CJ;
Journal of Biological Chemistry. 2003 278:1802-1806. doi: 10.1074/jbc.C200644200
PMID: 12446723

2002

A device for the high-pressure oxygenation of protein crystals.
Rutledge, PJ; Burzlaff, NI; Elkins, JM; Pickford, M; Baldwin, JE; Roach, PL;
Analytical Biochemistry. 2002 308:265-268. doi:
PMID: 12419338

Oligomeric structure of proclavaminic acid amidino hydrolase: evolution of a hydrolytic enzyme in clavulanic acid biosynthesis.
Elkins, JM; Clifton, IJ; Hernández, H; Doan, LX; Robinson, CV; Schofield, CJ; Hewitson, KS;
Biochemical Journal. 2002 366:423-434. doi: 10.1042/BJ20020125
PMID: 12020346

Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family.
Hewitson, KS; McNeill, LA; Riordan, MV; Tian, YM; Bullock, AN; Welford, RW; Elkins, JM; Oldham, NJ; Bhattacharya, S; Gleadle, JM; Ratcliffe, PJ; Pugh, CW; Schofield, CJ;
Journal of Biological Chemistry. 2002 277:26351-26355. doi: 10.1074/jbc.C200273200
PMID: 12042299

X-ray crystal structure of Escherichia coli taurine/α-ketoglutarate dioxygenase complexed to ferrous iron and substrates
Elkins, JM; Ryle, MJ; Clifton, IJ; Dunning Hotopp, JC; Lloyd, JS; Burzlaff, NI; Baldwin, JE; Hausinger, RP; Roach, PL;
Biochemistry. 2002 41:5185-5192. doi: 10.1021/bi016014e
PMID: 11955067

2001

Alternative oxidation by isopenicillin N synthase observed by X-ray diffraction.
Ogle, JM; Clifton, IJ; Rutledge, PJ; Elkins, JM; Burzlaff, NI; Adlington, RM; Roach, PL; Baldwin, JE;
Chemistry and Biology. 2001 8:1231-1237. doi:
PMID: 11755401

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