Dr Matthew Crump

Basic scientific research is not a guarantee of economic success; that requires the ability of firms to capture and commercialize the results. But it is an absolute requirement for economic success' Frank H. T. Rhodes from 'The creation of the future

Vacancies

NEW! April 6th 2011

Starting October 2011. 4 Year BBSRC Ph.D. Studentship in collaboration with UCB Biopharma

Investigation of the scope and limitations of capillary flow NMR as a medium throughput screening technology for generation of positional information in ligand-protein and protein-protein complexes.
 This project is the continuation of a highly successful collaboration which has already demonstrated that in principle mass spectrometry can be employed as a fast method for screening ligands which are weakly and non covalently bound to proteins of therapeutic interest with considerable potential in high throughput screening within the pharmaceutical industry. In parallel robust NMR methods have been developed for the timely delivery of structural information allowing rapid and informed follow up of hits identified by mass spectrometry. This project will build on this solid foundation in exploring the application of capillary flow NMR technology as a primary fragment screening tool. Further details including contact information can be found by Clicking here

Current group members.

Christopher Williams (Research Officer for NMR) Domain 11 project
1) Xu Dong (PhD - NMR protein Structure and function - novel ACP systems - joint with Tom Simpson)
2) Jennifer Hemmings (PhD - protein-ligand interactions - joint with Chris Willis)
3) Hannah Maple (PhD - protein-ligand interactions)
4) Mohammed Benama (H/D exchange to map antibody peptide interactions)
5) Kostas Vasilakis (PhD Protein-protein interactions)
6) Madeleine Strickland (PhD - IGF2R Domain 11 - in collaboration wth Prof. Bass Hassan - sponsored by Varian Inc.)
7) Roz Ellis (PhD - IGF2R and downstream enzymes) EPSRC
8) Supawadee Strithahan (PhD - Protein-protein interactions) Royal Thai Scholarship

Past members - 54 publications to date, total of four PhD completed students

Eliza Ploskon (Completed) Fatty acid ACP interactions with biosynthetic intermediates
Laura Rigau (Completed) PhD protein-drug interactions
Simon Evans (Completed) Anitbiotics - ACP research
Jed Long (Completed) Studies on Eotaxin-CCR3 peptide interactions

Research Outline

I am currently studying protein structure and function using principally NMR spectroscopy.  My main interest is the study of cancer related proteins using biological NMR. I am also interested in the polyketide synthase enzymes from Streptomycetes that are involved in the biosynthesis of numerous important antibiotics.   This research takes a structural approach to the problem. My other main areas of interest are the chemokine field and the application of NMR for screening potential small ligands for proteins of pharmaceutical interest. Increasingly we are also using X-ray crystallography for the structure determination of larger proteins.

Teaching

My NMR lectures can be found by clicking the following link

NMR lectures 2011
Publications (Updated April 6th, 2011)

60. Maple HJ, Garlish R, Whitcombe I, Taylor R, Crosby J, Crump MP (2011) XXX-XXX XXX In Preparation

59. Dong X, Williams C, Wattana-Amorn P, Thomas C, Crosby J, Crump MP (2011) XXX-XXX XXXSubmitted

58. Crump MP Hassan AB (2011) XXX-XXX XXX In Preparation

57. Shoemark DK, Fahey MS, Watson JJ, Tyler SJ, Hemmings JL, Bailey CD, Williams C, Jane DE, , Campos K, Williams C, Crump MP, Willis CL, Sessions RB, Dawbarn D and Allen SJ. (2011) XXX-XXX xxx xxxSubmitted

56. Dall'aglio P, Arthur CJ, Williams C, Vasilakis K, Maple HJ, Crosby J, Crump MP , Hadfield A (2011) XXX-XXX BiochemistryIn Press

55. Brown C, Campos-Leon K, Strickland M, Williams C, Fairweather V, Brady RL, Crump MP Gaston K (2011) Protein flexibility directs DNA recognition by the papillomavirus E2 proteins Nucleic Acid Research In Press

54. Ploskon E, Arthur CJ, Kanari A, Williams C, Crosby J, Willis C, Crump MP (2010) Recognition of intermediate functionality by acyl carrier protein over a complete cycle of fatty acid biosynthesis Chem. & Biol. 17:776-785

53. Wattana-Amorn P, Williams C, Cox RJ, Crosby J, Simpson TJ, Crump MP (2010) Solution structure of an acyl carrier protein domain from a fungal type I polyketide synthase Biochemistry 49:2186-2193

52. Bromley EHC, Channon KJ, King PJS, Mahmoud ZN, Banwell EF, Butler MF Crump MP , Dafforn TR, Hicks MR, Hirst JD, Rodger A, Wolfson DN (2010) Assembly pathways of a designed alpha-helical protein fiber Biophys J. 98: 1668-1676

51. Barwell N, Ferrand Y, Crump MP, Davis AP (2009) A synthetic lectin for beta-glucosyl Angew. Chemie. 48:7673-7676

50. Arthur CJ, Williams C, Pottage K, Ploskon E, Findlow ISC, Burston SG, Simpson TJ, Crosby J Crump MP (2009) Structure and malonyl CoA-ACP transacylase binding of Streptomyces coelicolor fatty acid synthase acyl carrier protei Chemical Biology 4:625-636

49. James MA, Mukherjee AJ, Crump MP, Gates PJ, Hoffman E, Robertson F, Pfalzner P, Evershed RP (2009) High prestige Royal Purple dyed textile from the bronze age royal tomb at Qatna, Syria. Antiquity 83:1109-1118

48. Gill FL, Crump MP, Schouten M, Bull ID. (2009) Lipid analysis of ground sloth coprolite Quat. Res.72:284-288

47. Evans SE, Williams C, Arthur CJ, Ploskon E, Wattana-amorn P, Cox RJ, Willis CL, Crosby J, Simpson TJ, Crump MP, (2009) Probing the interactions of early polyketide intermediates with the actinorhodin ACP from S. coelicolor A3(2). J. Mol. Biol.389:511-528

46. Beltran-Alvarez P, Arthur CJ, Cox RJ, Crosby J, Crump MP, Cox RJ (2009) Preliminary kinetic analysis of acyl carrier protein-ketosynthase interactions in the actinorhodin minimal polyketide synthase Mol. Biosystems 5:511-518

45. Rezgui D, Williams C, Zaccheo OJ, Savage S, Prince SN, Jones Y, Crump MP Hassan AB (2009) Structure and function of the human Gly1619Arg polymorphism of M6P/IGF2R domain 11 implicated in IGF2 dependent growth. Mol. Endocrinol.42:341-356

44. Ferrand Y, Klein E, Barwell NP, Crump MP, Jimenez-barbero, Vincent C, Ingale S, Boons G-J, Davis AP (2009) A synthetic lectin for O-linked beta-N-Acetylglucosamine Angew. Chemie 48:1175-1779

43. Castaldo G, Zucko J, Heidelberger S, Vujaklija D, Hranueli D, Wattana-Amorn P, Crump MP Crosby J, Long PF (2008) Proposed arrangement of proteins forming a bacterial type II polyketide synthase Chem. & Biol. 15:1156-1165

42. Kneissel S, Loveridge EJ, Williams C, Crump MP, Alleman RK (2008) Photocontrollable peptide-based switches target the anti-apoptopic protein Bcl-xL ChemBioChem 9:3046-3054

41. Evans S, Williams C, Arthur CJ, Burston SG, Simpson TJ, Crosby J, Williams C, Crump MP (2008) An ACP structural switch. Conformational differences between the apo and holo forms of the actinorhodin polyketide synthase acyl carrier protein. ChemBioChem 9:2424-2432

40. Scheschonka A, Findlow S, Schemm R, El Far O, Caldwell JH, Crump MP, Holden-Dye K, O'Connor V, Betz H, Werner JM Structural determinants of calmodulin binding to the intracellular C-terminal domain of the metabotropic glutamate receptor 7A (2008) J. Biol. Chem. 283:5577-5588

39. Halo LM, Marshall JW, Yakasai AA, Zhongshu S, Butts CP, Crump MP, Heneghan M, Bailey AM, Simpson TJ, Lazarus CM, Cox RJ (2008) Authentic Heterologous Expression Of The Tenellin Iterative Polyketide Synthase Non-Ribosomal Peptide Synthetase requires co-expression with an enoyl reductase ChemBioChem 9:585-594

38. Ploskon E, Arthur CJ, Evans SE, Williams C, Crosby J, Simpson TJ, Crump MP (2008) A mammalian type I fatty acid synthase acyl carrier protein domain does not sequester acyl chains J. Biol. Chem. 283:518-528

37. Ferrand Y, Crump MP, Davis AP (2007) A synthetic lectin analog for biomimetic disaccharide recognition Science 318:619-622

36. Williams C, Rezgui D, Prince SN, Zaccheo OJ, Foulstone EJ, Forbes BE, Norton RS, Crosby J, Hassan AB, Crump MP (2007) Structural insights into the interaction of Insulin-like growth factor2 with IGF2R domain 11 Structure 15:1065-1078

35. Wu J, Cooper SM, Cox RJ, Crosby J, Crump MP, Hothersall J, Sipron TJ, Thomas CM, Willis CL. (2007) Mupirocin H, a novel metabolite resulting from mutation of the HMG-CoA synthase analogue, mupH in Pseudomonas Flourescens Chem. Comm. 20:2040-2042

34. Slupsky CM, Spyracopoulos L, Booth VK, Sykes BD, Crump MP, (2007) Probing nascent structures in peptides using natural abundance 13C NMR relaxation and reduced spectral density mapping. Proteins - Struct., Funct. and Genet. 67:18-30

33. Gordon AH, Lindsay DM, Promaswan N, Simpson G, Crump MP, , Mulholland K, Hayter BR, Gallagher T. (2006) Glycosylated Foldamers as Probes to Elicit the Molecular Detail of Carbohydrate-Carbohydrate Interactions J. Am. Chem. Soc.,128:10638-10639

32. Szafranska A, Arthur CJ, Reid M, Findlow SC, Long J, Simpson TJ, Crump MP, Crosby J (2006) The malonyl transferase activity of polyketide synthase acyl carrier proteins Chem. Biol.,13:587-596

31. Zaccheo OJ, Prince Sn, Miler DM, Williams C, Brown J, Jones Y, Crump MP, Hassan An (2006) Kinetics of Insulin-like growth factor II (IGF-II) interaction with domain 11 residues of the IGF-II/Mannose-6-phosphate receptor; Identification of binding site positive and negative regulators. J. Mol. Biol.,359:403-421

30. Arthur CJ, Szfranska A, Evans S, Findlow SC, Burston SG, Owen P, Clark-Lewis I, Simpson TJ, Crosby J, Crump MP, (2005) Self-malonylation is an intrinsic property of a chemically synthesized Type II polyketide acyl carrier protein. Biochemistry,44:15414-15421

29. Cooper SM, Cox RJ, Crosby J, Crump MP, Hothersall J, Laosripaiboon W, Simpson TJ, Thomas CM (2005) Mupirocin W, a Novel Pseudomonic Acid Produced by Targeted Mutation of the Mupirocin Biosynthetic Gene Cluster. Chem. Commun.,9:1179-1181

28. Klein, E., Crump MP, Davis, AP.. (2005) Carbohydrate recognition in water by a tricyclic polyamide receptor Angew. Chemie,44:298-302

27. Parker CA, Anderson NJ, Robinson ESJ, Price R, Tyacke RJ, Husbands SM, Dillon MP, Eglen RM, Hudson AL, Nutt DJ, Crump MP, Crosby J. (2004) Harman and Harmalan are the bioactive components of classical clonidine displacing substance. Biochemistry,43:16385-16392

26. Hadfield AT, Limpkin C, Teartasin W, Simpson TJ, Crosby J, Crump MP Crump MP, (2004) The Crystal Structure of the Actinorhodin Polyketide Reductase (actIII): Proposed mechanism for ACP and Polyketide Binding. Structure,12:1865-1875

25. Teartasin W, Limpkin C, Glod F, Spencer J, Cox Russell, Crosby J, Crump MP, , Hadfield A (2004) Expression, purification and preliminary X-ray diffraction analysis of a ketoreductase from a Type II polyketide synthase. Acta Cryst.,D60:1137-1138

24. Crump MP, ,Ceska TA, Spyracopoulos L, Henry A, Archibald SC, Alexander R, Taylor RJ, Findlow SC, O' Connell J, Robinson MK, Shock A (2004) The structure of an allosteric inhibitor of LFA-1 bound to the I-domain studied by crystallography, NMR and calorimetry. Biochemistry,43:2394-2404

23. Findlow IS, Winsor C, Simpson TJ, Crosby J, Crump MP, (2003) Solution structure and dynamics of Oxytetracycline polyketide synthase ACP from S. rimosus Biochemistry.42:8423-8433

22. Housden HR, Skipp PJS, Crump MP, Broadbridge RJ, Crabbe T, Perry MJ, Gore MG (2003) Evidence for plasticity and structural mimicry at the immunoglobulin light chain-protein L interface Eur. J. Biochem..270:2369-2376

21. Reed MAC, Schweizer M, Szafranska AE, Arthur C, Nicholson TP, Cox RJ, Crosby J, Crump MP, Simpson TJ (2003) The type I rat fatty acid synthase ACP shows structural homology and analogous biochemical properties to Type II ACPs Org. Biomol. Chem..1:463-471

20. Graille M, Harrison S, Crump MP, Findlow SC, Housden NG, Muller BH, Battail-poirot N, Sibai G, Sutton BJ, Taussig MJ Jolivet-Reynaud C, Gore MG, Stura EA. (2002) Evidence for plasticity and structural mimicry at the immunoglobulin light chain-protein L interface J. Biol. Chem..277:47500-47506

19. Coates L., Erskine PT, Crump MP, Wood SP, Cooper JB. (2002) Five atomic resolution structures of endothiapepsin inhibitor complexes; implications for the aspartic proteinase mechanism. J. Mol. Biol. 318:1405-1415.

18. Spyracopoulos L, Lavigne P, Crump MP, Gagni SM, Kay CM, Sykes BD (2001) Temperature dependence of dynamics and thermodynamics of the regulatory domain of human cardiac troponin C. Biochemistry 40:12541-12551.

17. Shoolingin-Jordan, PM., Crump, MP. (2001) Phosphopantetheine dependent enzymes. Encyclopedia of Life Sciences. www.els.net (electronic publication).

16. Crump, MP. Shoolingin-Jordan, PM (2001) CoA dependent enzymes. Encyclopedia of Life Sciences.  www.els.net (electronic publication).

15. Keizer DW, Slupsky CM, Kalisiak, M, Campbell AM, Crump MP, Sastry PA, Hazes B, Irvin RT, Sykes, BD. (2001) Structure of a Pilin Monomer from Pseudomonas aeruginosa: Implications for the assembly of Pili. J. Biol. Chem. 276:24186-24193.

14. Keizer DW., Kalisiak, M., Crump, MP., Suh, J-H., Irvin RT., Sykes, BD. (2001) Assignments of 1H and 15N resonances of the Pseudomonas aeruginosa K122-4 pilin monomer J. Biomol. NMR. 19:385-386.

13. Crump MP, Elisseeva, E., Gong, J-H., Clark-Lewis, I., Sykes BD (2001) Structure/Function of Human Herpesvirus-8 MIP-II (1-71) and the antagonist N-terminal segment (1-10) FEBS Lett. FEBS Lett.489:171-175.

12. Elisseeva EL., Slupsky CM., Crump MP, Clark-Lewis I., Sykes BD (2000) NMR studies of Active N-terminal peptides of Stromal Cell-derived Factor-1 J. Biol. Chem.

11. Keizer, DW, Crump MP, Slupsky CM., Lee, T-W., Clark-Lewis, I, Sykes, BD (2000) Solution structure of the human CC chemokine, I-309: A chemokine with three disulfide bonds. Biochemistry 39, 6053-6059

10. Crump MP, Spyracopolous L, Lavigne P, Kim K-S, Clark-Lewis I, Sykes BD. (1999) Backbone dynamics of the human chemokine eotaxin: Fast motions, slow motions and possible implications for receptor binding. Protein Science 8:2041-2054.

9. Rajarathnam K., Crump MP, Clark-Lewis I, Sykes BD (1999) Spectroscopic Characterization of Chemokines: Relevance for Quality Control and Standardization In Biological Characterization and Assay of Cytokines and Growth Factors. Dev Biol Stand., Brown, F., Mire-Sluis, A.R. (eds) Karger, Basel, Switzerland, Volume 97: 49-57.

8. Crump MP, Rajarathnam K, Kim K-S, Clark-Lewis I, Sykes BD. (1998) Solution structure of eotaxin, a chemokine that selectively recruits eosinophils in allergic inflammation. J. Biol. Chem. 273:22471-22479.

7. Crosby J, Byrom KJ, , Hitchman TS, Cox RJ, Crump MP, Findlow SC, Bibb MJ, Simpson TJ. (1998) Acylation of Streptomyces Type II polyketide synthase acyl carrier proteins. FEBS Lett, 433:132-138.

6. Lavigne P, Crump MP, Gagni SM, Hodges RS, Kay CM, Sykes BD. (1998) Insights into the mechanism of heterodimerisation from the 1H-NMR solution structure of the c-Myc-Max heterodimeric leucine zipper. J. Mol. Biol. 281:165-181.

5. Crump MP, Gong J-H, Loetscher P, Rajarathnam K, Amara A, Arenzana-Seisdedos F, Virelizier J-L, Baggiolini M, Sykes BD, Clark-Lewis I. (1997) Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1. EMBO J. 16:6996-7007.

4. Crump MP, Crosby J, Dempsey CE, Parkinson JA, Murray M, Hopwood DA, Simpson TJ. (1997) Solution structure of the Actinorhodin polyketide synthase acyl carrier protein from Streptomyces coelicolor A3(2). Biochemistry 36:6000-6008.

3. Lavigne P, Crump MP, Gagni S, Sykes BD, Kay C. (1997) 1H NMR evidence for two buried Asn side-chains in the c-Myc-Max Heterodimeric a-helical coiled coil. Techniques in Protein Chemistry Vol VIII, 617-623.

2. Crump MP, Crosby, J, Dempsey CE, Murray M, Hopwood DA, Simpson TJ. 1996 The Polyketide Acyl Carrier Protein from Streptomyces coelicolor A3(2) and the E. coli Fatty Acid ACP show conserved Secondary Structure. FEBS Lett. 391, 302-306.

1. Crump MP (1995) Structural Studies on the Type II polyketide acyl carrier proteins. Ph.D. Thesis, University of Bristol.