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John E. Ladbury, Ph.D., M.Sc., B.Sc.

Present Title & Affiliation

Primary Appointment

Professor, Department of Biochemistry and Molecular Biology, Division of Basic Science Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX

Research Interests

 

Specificity in Tyrosine Kinase-Mediated Signal Transduction – A Cellular to Atomic Level Investigation.

Eukaryotic cells react to the external environment through interaction with membrane-bound receptors. Distinct types of receptors respond to different stimuli, but all are capable of sensing a binding event outside, and initiating signal transduction inside the cell. Most fundamental cellular processes including the cell cycle, migration, differentiation, survival, proliferation, immune response and metabolism are transduced through receptor tyrosine kinase (RTK)-mediated signal transduction. For transduction without corruption, the protein-protein interactions involved have to produce mutually exclusive responses. Aberrancies in these pathways are responsible for many disease states including cancer, immunodeficiency and diabetes. Many of the signalling pathways emanating from RTKs involve interactions of distinct domains (e.g. SH2, SH3, PTB). Our data suggest that binding of these domains to cognate ligands are not sufficiently specific to ensure mutual exclusivity of signalling. We are thus investigating alternative ways in which the integrity of a signal from a RTK can be maintained. Focusing on early signalling events (within 1 hour of stimulation) we are exploring the structural, biophysical, and cellular outcomes of protein complex formation at the receptor. Perturbation of these complexes by inhibiting assembly or modifying the time course (by making mutations) reveals how the exquisite sensitivity of early signalling complex formation can ensure specificity. Furthermore, understanding the way in which these complexes modulate signaling networks provides insight into novel route to pharmaceutical intervention.

 

  

Office Address

The University of Texas MD Anderson Cancer Center
6767 Bertner St.
Unit Number: 1000
Houston, TX
Room Number: BSRB, 7.8136A
Phone: 713/792-3570
Fax: 713/720-0855
Email: JELadbury@mdanderson.org

Education & Training

Degree-Granting Education

1990 University of Greenwich, London, United Kingdom, PHD, Polymer Chemistry
1988 Polytechnic of Central London (London School of Management), London, United Kingdom, Cert. Dip. Accntng & Finance, Accounting & Finance
1987 Polytechnic of Central London (London School of Management), London, United Kingdom, Dip. Management Studies, Distinction, Management
1987 University of Greenwich, London, United Kingdom, MS, Distinction, Chemical Analysis
1982 University of London, London, United Kingdom, BS, Honours, Chemistry/Physics

Postgraduate Training

1994-1995 Research Fellowship, New York University Medical Center, New York, NY, Prof. J Schlessinger
1993-1994 Research Fellowship, Harvard University Medical School, Boston, MA, Prof. MA Weiss
1990-1993 Research Fellowship, Yale University, New Haven, CT, Prof. JM Sturtevant

Experience/Service

Administrative Appointments/Responsibilities

Director, Center for Biomolecular Structure and Function (CBSF), The University of Texas M. D. Anderson Cancer Center, Houston, TX, 2009

Endowed Positions

Edward Rotan Distinguished Professor in Cancer Research, Department of Biochemistry and Molecular Biology, Division of Basic Science Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 2008

Honors and Awards

2003-2008 Wellcome Trust Senior Research Fellow (Renewed), Wellcome Trust
1998-present Chartered Chemist/Chartered Scientist, Royal Society of Chemistry
1998-present Member of the Royal Society of Chemistry, Royal Society of Chemistry
1998-2003 Wellcome Trust Senior Research Fellow, Wellcome Trust
1994-1998 Wellcome Trust Research Career Development Fellowship, Wellcome Trust
1994-1997 Junior Research fellow, Somerville College, Oxford, Somerville College
1989 Perkin-Elmer Travel Scholarship
1989 Society of the Chemical Industry Travel Scholarship., Society of the Chemical Industry
1988-1992 Member Chartered Association of Certified Accountants, Chartered Association of Certified Accountants
1987-1990 Ministry of Defence Research Scholar
1987 Dun & Bradstreet Award

Selected Publications

Peer-Reviewed Original Research Articles

1. Chen Z, Vohidov F, Coughlin JM, Stagg LJ, Arold ST, Ladbury JE, Ball ZT. Catalytic protein modification with dirhodium metallopeptides: specificity in designed and natural systems. J Am Chem Soc 134(24):10138-10145, 6/20/2012. e-Pub 6/7/2012. PMID: 22621321.
2. Lin CC, Melo FA, Ghosh R, Suen KM, Stagg LJ, Kirkpatrick J, Arold ST, Ahmed Z, Ladbury JE. Inhibition of Basal FGF Receptor Signaling by Dimeric Grb2. Cell 149(7):1514-24, 6/22/2012. PMID: 22726438.
3. Di Domizio J, Zhang R, Stagg LJ, Gagea M, Zhuo M, Ladbury JE, Cao W. Binding with nucleic acids or glycosaminoglycans converts soluble protein oligomers to amyloid. J Biol Chem 287(1):736-47, 1/2/2012. e-Pub 11/18/2011. PMCID: PMC3249128.
4. Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat J-P, Nickerson E, Auclair D, Li L, Place C, DiCara D, Ramos AH, Lawrence MS, Cibulskis K, Sivachenko A, Voet D, Saksena G, Stransky N, Onofrio RC, Winckler W, Ardlie K, Wagle N, Wargo J, Chong K, Morton DL, Stemke-Hale K, Chen G, Noble M, Meyerson M, Ladbury JE, Davies MA, Gerschenwald JE, Wagner SN, Hoon DSB, Schadendorf D, Lander ES, Gabriel SB, Getz G, Garraway LA,Chin, L. A Landscape of driver mutations in melanoma. Cell 150:251-263, 2012.
5. Ramakrishnan M, Melo FA, Kinsey BM, Ladbury JE, Kosten TR, Orson FM. Probing cocaine-antibody interactions in buffer and human serum. PLoS One e40518:1-12, 2012.
6. Olsson TS, Ladbury JE, Pitt WR, Williams MA. Extent of enthalpy-entropy compensation in protein-ligand interactions. Protein Sci 20(9):1607-18, 9/2011. e-Pub 8/2/2011. PMCID: PMC3190155.
7. Philippe D, Ababou A, Yang X, Ghosh R, Daviter T, Ladbury JE, Pfuhl M. Making ends meet: the importance of the N- and C-termini for the structure, stability, and function of the third SH3 domain of CIN85. Biochemistry 50(18):3649-59, 5/10/2011. e-Pub 4/12/2011. PMID: 21446695.
8. Yu C, Sonnen AF, George R, Dessailly BH, Stagg LJ, Evans EJ, Orengo CA, Stuart DI, Ladbury JE, Ikemizu S, Gilbert RJ, Davis SJ. Rigid-body ligand recognition drives cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor triggering. J Biol Chem 286(8):6685-96, 2/25/2011. e-Pub 12/14/2010. PMCID: PMC3057841.
9. Frenkel M, Chirico RD, Diky V, Brown PL, Dymond JH, Goldberg RN, Goodwin ARH, Heerklotz H, Königsberger E, Ladbury JE, Marsh KN, Remata DP, Stein SE, Wakeham WA, Williams PA. Extension of ThermoML: The IUPAC standard for thermodynamic data communications (IUPAC Recommendations 2011). Pure and Applied Chemistry 83:1935-1967, 2011.
10. Chirico RD, Frenkel M, Diky V, Goldberg RN, Heerklotz H, Ladbury JE, Remeta DP, Dymond JH, Goodwin ARH, Marsh KN, Wakeham WA. ThermoML – an XML-based approach for storage and exchange of experimental and critically evaluated thermophysical and thermochemical property data. 4. Biomaterials. Journal of Chemical and Engineering Data 55:1564-1572, 2011.
11. Arold ST, Leonard PG, Parkinson GN, Ladbury JE. H-NS forms a super-helical protein scaffold for DNA condensation. Proc Natl Acad Sci U S A 107(36):15728-15732, 9/7/2010. e-Pub 8/23/2010. PMCID: PMC2936596.
12. Stevens CN, Simeone AM, John S, Ahmed Z, Lucherini OM, Baldari CT, Ladbury JE. T-cell receptor early signalling complex activation in response to interferon-alpha receptor stimulation. Biochem J 428(3):429-37, 6/15/2010. e-Pub 5/27/2010. PMCID: PMC2888567.
13. Raab M, Wang H, Lu Y, Smith X, Wu Z, Strebhardt K, Ladbury JE, Rudd CE. T cell receptor "inside-out" pathway via signaling module SKAP1-RapL regulates T cell motility and interactions in lymph nodes. Immunity 32(4):541-56, 4/23/2010. e-Pub 3/25/2010. PMID: 20346707.
14. Leonard PG, Parkinson GN, Gor J, Perkins SJ, Ladbury JE. The absence of inorganic salt is required for the crystallization of the complete oligomerization domain of Salmonella typhimurium histone-like nucleoid-structuring protein. Acta Crystallogr Sect F Struct Biol Cryst Commun 66(Pt 4):421-5, 4/1/2010. e-Pub 3/31/2010. PMCID: PMC2852335.
15. Ladbury JE, Klebe G, Freire E. Adding calorimetric data to decision making in lead discovery: a hot tip. Nat Rev Drug Discov 9(1):23-7, 1/2010. e-Pub 12/2009. PMID: 19960014.
16. Ahmed Z, George R, Lin CC, Suen KM, Levitt JA, Suhling K, Ladbury JE. Direct binding of Grb2 SH3 domain to FGFR2 regulates SHP2 function. Cell Signal 22(1):23-33, 1/2010. e-Pub 9/6/2009. PMID: 19735729.
17. George, R., Chan, H. –L., Ahmed Z, Suen KM, Stevens CN, Levitt JA, Suhling K, Timms J, Ladbury JE. A complex of Shc and Ran-GTPase localises to the cell nucleus. Cellular and Molecular Life Sciences 66:711-720, 1/2009.
18. Zhou L, Li J, George R, Ruchaud S, Zhou H–G, Ladbury JE, Earnshaw WC, Yuan X. Effects of full length borealin on the composition and protein-protein interaction activity of a binary passenger complex. Biochemistry 48:1156-1161, 1/2009.
19. Leonard, P. G., Ono, S., Gor, J., Perkins, S. J. & Ladbury, J. E. Investigation of the self-association and hetero-association interactions of H-NS and StpA from Enterobacteria. Molecular Microbiology 73:165-179, 2009.
20. Ababou, A., Pfuhl, M. & Ladbury J. E. Novel insights into binding mechanisms of CIN85 SH3 domains to Cbl proteins: solution-based investigations and in vivo implications. Journal of Molecular Biology 387:1120-1136, 2009.
21. Nilapwar, S., Williams, E., Fu, C., Prodromou, C., Pearl, L. H., Williams, M. A. & Ladbury, J. E. Structural-thermodynamic relationships of interactions in the N-terminal ATP-binding domain of Hsp90. Journal of Molecular Biology 392:923-936, 2009.
22. Schüller AC, Ahmed Z, Levitt JA, Suen KM, Suhling K, Ladbury JE. Indirect recruitment of the signalling adaptor Shc to the fibroblast growth factor receptor 2 (FGFR2). Biochem J 416(2):189-99, 12/1/2008. PMID: 18840094.
23. Taylor JD, Ababou A, Fawaz RR, Hobbs CJ, Williams MA, Ladbury JE. Structure, dynamics, and binding thermodynamics of the v-Src SH2 domain: implications for drug design. Proteins 73(4):929-40, 12/2008. PMID: 18536014.
24. Olsson TS, Williams MA, Pitt WR, Ladbury JE. The thermodynamics of protein-ligand interaction and solvation: insights for ligand design. J Mol Biol 384(4). e-Pub 10/9/2008. PMID: 18930735.
25. Ababou A, Pfuhl M, Ladbury JE. The binding stoichiometry of CIN85 SH3 domain A and Cbl-b. Nat Struct Mol Biol 15(9):890-1; author reply 891-2, 9/2008. PMID: 18769462.
26. Patel S, George R, Autore F, Fraternali F, Ladbury JE, Nikolova PV. Molecular interactions of ASPP1 and ASPP2 with the p53 protein family and the apoptotic promoters PUMA and Bax. Nucleic Acids Res 36(16). e-Pub 8/2/2008. PMCID: PMC2532732.
27. Ahmed Z, Schüller AC, Suhling K, Tregidgo C, Ladbury JE. Extracellular point mutations in FGFR2 elicit unexpected changes in intracellular signalling. Biochem J 413(1):37-49, 7/1/2008. PMID: 18373495.
28. Schüller AC, Ahmed Z, Ladbury JE. Extracellular point mutations in FGFR2 result in elevated ERK1/2 activation and perturbation of neuronal differentiation. Biochem J 410(1):205-11, 2/15/2008. PMID: 18039182.
29. George R, Schuller AC, Harris R, Ladbury JE. A phosphorylation-dependent gating mechanism controls the SH2 domain interactions of the Shc adaptor protein. J Mol Biol 377(3). e-Pub 12/28/2007. PMID: 18279888.
30. Taylor JD, Gilbert PJ, Williams MA, Pitt WR, Ladbury JE. Identification of novel fragment compounds targeted against the pY pocket of v-Src SH2 by computational and NMR screening and thermodynamic evaluation. Proteins 67(4):981-90, 6/1/2007. PMID: 17393456.
31. Impagliazzo A, Blok AJ, Cliff MJ, Ladbury JE, Ubbink M. Redox-state-dependent complex formation between pseudoazurin and nitrite reductase. J Am Chem Soc 129(1):226-33, 1/10/2007. PMID: 17199303.
32. Evans EJ, Castro MA, O'Brien R, Kearney A, Walsh H, Sparks LM, Tucknott MG, Davies EA, Carmo AM, van der Merwe PA, Stuart DI, Jones EY, Ladbury JE, Ikemizu S, Davis SJ. Crystal structure and binding properties of the CD2 and CD244 (2B4)-binding protein, CD48. J Biol Chem 281(39):29309-20, 9/29/2006. e-Pub 6/27/2006. PMID: 16803907.
33. Beuron F, Dreveny I, Yuan X, Pye VE, McKeown C, Briggs LC, Cliff MJ, Kaneko Y, Wallis R, Isaacson RL, Ladbury JE, Matthews SJ, Kondo H, Zhang X, Freemont PS. Conformational changes in the AAA ATPase p97-p47 adaptor complex. EMBO J 25(9):1967-76, 5/3/2006. e-Pub 4/6/2006. PMCID: PMC1456939.
34. Zavaleta J, Chinchilla DB, Ramirez A, Pao A, Martinez K, Nilapwar S, Ladbury JE, Mallik S, Gomez FA. Partial filling multiple injection affinity capillary electrophoresis (PFMIACE) to estimate binding constants of receptors to ligands. Talanta 71(1). e-Pub 5/15/2006. PMID: 19071288.
35. Cliff MJ, Harris R, Barford D, Ladbury JE, Williams MA. Conformational diversity in the TPR domain-mediated interaction of protein phosphatase 5 with Hsp90. Structure 14(3):415-26, 3/2006. PMID: 16531226.
36. Grunau A, Paine MJ, Ladbury JE, Gutierrez A. Global effects of the energetics of coenzyme binding: NADPH controls the protein interaction properties of human cytochrome P450 reductase. Biochemistry 45(5):1421-34, 2/7/2006. PMID: 16445284.
37. Zavaleta J, Chinchilla DB, Kaddis CF, Martinez K, Brown A, Gomez A, Pao A, Ramirez A, Nilapwar S, Ladbury JE, Gomez FA. Partial-filling affinity capillary electrophoresis techniques to probe the binding of glycopeptide antibiotics to D-Ala-D-Ala terminus peptides. J Capill Electrophor Microchip Technol 9(5-6):101-17, 2006. PMID: 17094294.
38. Ahmed Z, Beeton CA, Williams MA, Clements D, Baldari CT, Ladbury JE. Distinct spatial and temporal distribution of ZAP70 and Lck following stimulation of interferon and T-cell receptors. J Mol Biol 353(5):1001-10, 11/11/2005. e-Pub 9/27/2005. PMID: 16219325.
39. Ono S, Goldberg MD, Olsson T, Esposito D, Hinton JC, Ladbury JE. H-NS is a part of a thermally controlled mechanism for bacterial gene regulation. Biochem J 391(Pt 2):203-13, 10/15/2005. PMCID: PMC1276917.
40. Taylor JD, Fawaz RR, Ababou A, Williams MA, Ladbury JE. NMR assignment of the apo and peptide-bound SH2 domain from the Rous sarcoma viral protein Src. J Biomol NMR 32(4):339, 8/2005. PMID: 16211495.
41. Cliff MJ, Williams MA, Brooke-Smith J, Barford D, Ladbury JE. Molecular recognition via coupled folding and binding in a TPR domain. J Mol Biol 346(3):717-32, 2/25/2005. e-Pub 1/18/2005. PMID: 15713458.
42. Yang J, Roe SM, Cliff MJ, Williams MA, Ladbury JE, Cohen PT, Barford D. Molecular basis for TPR domain-mediated regulation of protein phosphatase 5. EMBO J 24(1):1-10, 1/12/2005. e-Pub 12/2/2004. PMCID: PMC544909.
43. Erra E, Petraccone L, Esposito V, Randazzo A, Mayol L, Ladbury J, Barone G, Giancola C. Interaction of porphyrin with G-quadruplex structures. Nucleosides Nucleotides Nucleic Acids 24(5-7):753-6, 2005. PMID: 16248030.
44. Keatch SA, Leonard PG, Ladbury JE, Dryden DT. StpA protein from Escherichia coli condenses supercoiled DNA in preference to linear DNA and protects it from digestion by DNase I and EcoKI. Nucleic Acids Res 33(20):6540-6, 2005. PMCID: PMC1289078.
45. Lachenmann MJ, Ladbury JE, Qian X, Huang K, Singh R, Weiss MA. Solvation and the hidden thermodynamics of a zinc finger probed by nonstandard repair of a protein crevice. Protein Sci 13(12):3115-26, 12/2004. PMCID: PMC2287320.
46. Lachenmann MJ, Ladbury JE, Dong J, Huang K, Carey P, Weiss MA. Why zinc fingers prefer zinc: ligand-field symmetry and the hidden thermodynamics of metal ion selectivity. Biochemistry 43(44):13910-25, 11/9/2004. PMID: 15518539.
47. Bergqvist S, Williams MA, O'Brien R, Ladbury JE. Heat capacity effects of water molecules and ions at a protein-DNA interface. J Mol Biol 336(4):829-42, 2/27/2004. PMID: 15095863.
48. Kowanetz K, Szymkiewicz I, Haglund K, Kowanetz M, Husnjak K, Taylor JD, Soubeyran P, Engstrom U, Ladbury JE, Dikic I. Identification of a novel proline-arginine motif involved in CIN85-dependent clustering of Cbl and down-regulation of epidermal growth factor receptors. J Biol Chem 278(41):39735-46, 10/10/2003. e-Pub 7/21/2003. PMID: 12874286.
49. Esposito D, Petrovic A, Harris R, Ono S, Eccleston JF, Mbabaali A, Haq I, Higgins CF, Hinton JC, Driscoll PC, Ladbury JE. H-NS oligomerization domain structure reveals the mechanism for high order self-association of the intact protein. J Mol Biol 324(4):841-50, 12/6/2002. PMID: 12460581.
50. Flatman R, McLauchlan WR, Juge N, Furniss C, Berrin JG, Hughes RK, Manzanares P, Ladbury JE, O'Brien R, Williamson G. Interactions defining the specificity between fungal xylanases and the xylanase-inhibiting protein XIP-I from wheat. Biochem J 365(Pt 3):773-81, 8/1/2002. PMCID: PMC1222710.
51. Salek RM, Williams MA, Prodromou C, Pearl LH, Ladbury JE. Backbone resonance assignments of the 25kD N-terminal ATPase domain from the Hsp90 chaperone. J Biomol NMR 23(4):327-8, 8/2002. PMID: 12398355.
52. Low LY, Hernández H, Robinson CV, O'Brien R, Grossmann JG, Ladbury JE, Luisi B. Metal-dependent folding and stability of nuclear hormone receptor DNA-binding domains. J Mol Biol 319(1):87-106, 5/24/2002. PMID: 12051939.
53. Bergqvist S, Williams MA, O'Brien R, Ladbury JE. Reversal of halophilicity in a protein-DNA interaction by limited mutation strategy. Structure 10(5):629-37, 5/2002. PMID: 12015146.
54. Lachenmann MJ, Ladbury JE, Phillips NB, Narayana N, Qian X, Weiss MA. The hidden thermodynamics of a zinc finger. J Mol Biol 316(4):969-89, 3/1/2002. PMID: 11884136.
55. Haq I, O'Brien R, Lagunavicius A, Siksnys V, Ladbury JE. Specific DNA recognition by the type II restriction endonuclease MunI: the effect of pH. Biochemistry 40(49):14960-7, 12/11/2001. PMID: 11732916.
56. Lee L, Stollar E, Chang J, Grossmann JG, O'Brien R, Ladbury J, Carpenter B, Roberts S, Luisi B. Expression of the Oct-1 transcription factor and characterization of its interactions with the Bob1 coactivator. Biochemistry 40(22):6580-8, 6/5/2001. PMID: 11380252.
57. Henriques DA, Ladbury JE. Inhibitors to the Src SH2 domain: a lesson in structure--thermodynamic correlation in drug design. Arch Biochem Biophys 390(2):158-68, 6/15/2001. PMID: 11396918.
58. Arold ST, Ulmer TS, Mulhern TD, Werner JM, Ladbury JE, Campbell ID, Noble ME. The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases. J Biol Chem 276(20):17199-205, 5/18/2001. e-Pub 2/2/2001. PMID: 11278857.
59. Joseph C, Stier G, O'Brien R, Politou AS, Atkinson RA, Bianco A, Ladbury JE, Martin SR, Pastore A. A structural characterization of the interactions between titin Z-repeats and the alpha-actinin C-terminal domain. Biochemistry 40(16):4957-65, 4/24/2001. PMID: 11305911.
60. Renzoni D, Esposito D, Pfuhl M, Hinton JC, Higgins CF, Driscoll PC, Ladbury JE. Structural characterization of the N-terminal oligomerization domain of the bacterial chromatin-structuring protein, H-NS. J Mol Biol 306(5):1127-37, 3/9/2001. PMID: 11237622.
61. Bergqvist S, O'Brien R, Ladbury JE. Site-specific cation binding mediates TATA binding protein-DNA interaction from a hyperthermophilic archaeon. Biochemistry 40(8):2419-25, 2/27/2001. PMID: 11327862.
62. Payne JW, Grail BM, Gupta S, Ladbury JE, Marshall NJ, O'Brien R, Payne GM. Structural basis for recognition of dipeptides by peptide transporters. Arch Biochem Biophys 384(1):9-23, 12/1/2000. PMID: 11147841.
63. Henriques DA, Ladbury JE, Jackson RM. Comparison of binding energies of SrcSH2-phosphotyrosyl peptides with structure-based prediction using surface area based empirical parameterization. Protein Sci 9(10):1975-85, 10/2000. PMCID: PMC2144457.
64. Pacini S, Valensin S, Telford JL, Ladbury J, Baldari CT. Temporally regulated assembly of a dynamic signaling complex associated with the activated TCR. Eur J Immunol 30(9):2620-31, 9/2000. PMID: 11009096.
65. Prodromou C, Panaretou B, Chohan S, Siligardi G, O'Brien R, Ladbury JE, Roe SM, Piper PW, Pearl LH. The ATPase cycle of Hsp90 drives a molecular 'clamp' via transient dimerization of the N-terminal domains. EMBO J 19(16):4383-92, 8/15/2000. PMCID: PMC302038.
66. Kahmann JD, O'Brien R, Werner JM, Heinegârd D, Ladbury JE, Campbell ID, Day AJ. Localization and characterization of the hyaluronan-binding site on the link module from human TSG-6. Structure 8(7):763-74, 7/15/2000. PMID: 10903951.
67. Lundbäck T, Chang JF, Phillips K, Luisi B, Ladbury JE. Characterization of sequence-specific DNA binding by the transcription factor Oct-1. Biochemistry 39(25):7570-9, 6/27/2000. PMID: 10858307.
68. Smyth CP, Lundbäck T, Renzoni D, Siligardi G, Beavil R, Layton M, Sidebotham JM, Hinton JC, Driscoll PC, Higgins CF, Ladbury JE. Oligomerization of the chromatin-structuring protein H-NS. Mol Microbiol 36(4):962-72, 5/2000. PMID: 10844682.
69. O'Brien R, Rugman P, Renzoni D, Layton M, Handa R, Hilyard K, Waterfield MD, Driscoll PC, Ladbury JE. Alternative modes of binding of proteins with tandem SH2 domains. Protein Sci 9(3):570-9, 3/2000. PMCID: PMC2144564.
70. Rostom AA, Tame JR, Ladbury JE, Robinson CV. Specificity and interactions of the protein OppA: partitioning solvent binding effects using mass spectrometry. J Mol Biol 296(1):269-79, 2/11/2000. PMID: 10656831.
71. Chung EW, Henriques DA, Renzoni D, Morton CJ, Mulhern TD, Pitkeathly MC, Ladbury JE, Robinson CV. Probing the nature of interactions in SH2 binding interfaces--evidence from electrospray ionization mass spectrometry. Protein Sci 8(10):1962-70, 10/1999. PMCID: PMC2144146.
72. Sleigh SH, Seavers PR, Wilkinson AJ, Ladbury JE, Tame JR. Crystallographic and calorimetric analysis of peptide binding to OppA protein. J Mol Biol 291(2):393-415, 8/13/1999. PMID: 10438628.
73. Chang JF, Phillips K, Lundbäck T, Gstaiger M, Ladbury JE, Luisi B. Oct-1 POU and octamer DNA co-operate to recognise the Bob-1 transcription co-activator via induced folding. J Mol Biol 288(5):941-52, 5/21/1999. PMID: 10329190.
74. Baraldi E, Djinovic Carugo K, Hyvönen M, Surdo PL, Riley AM, Potter BV, O'Brien R, Ladbury JE, Saraste M. Structure of the PH domain from Bruton's tyrosine kinase in complex with inositol 1,3,4,5-tetrakisphosphate. Structure 7(4):449-60, 4/15/1999. PMID: 10196129.
75. Willcox BE, Gao GF, Wyer JR, Ladbury JE, Bell JI, Jakobsen BK, van der Merwe PA. TCR binding to peptide-MHC stabilizes a flexible recognition interface. Immunity 10(3):357-65, 3/1999. PMID: 10204491.
76. Prodromou C, Siligardi G, O'Brien R, Woolfson DN, Regan L, Panaretou B, Ladbury JE, Piper PW, Pearl LH. Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones. EMBO J 18(3):754-62, 2/1/1999. PMCID: PMC1171168.
77. Roe SM, Prodromou C, O'Brien R, Ladbury JE, Piper PW, Pearl LH. Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J Med Chem 42(2):260-6, 1/28/1999. PMID: 9925731.
78. Arold S, O'Brien R, Franken P, Strub MP, Hoh F, Dumas C, Ladbury JE. RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef. Biochemistry 37(42):14683-91, 10/20/1998. PMID: 9778343.
79. Chung E, Henriques D, Renzoni D, Zvelebil M, Bradshaw JM, Waksman G, Robinson CV, Ladbury JE. Mass spectrometric and thermodynamic studies reveal the role of water molecules in complexes formed between SH2 domains and tyrosyl phosphopeptides. Structure 6(9):1141-51, 9/15/1998. PMID: 9753693.
80. Panaretou B, Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW, Pearl LH. ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo. EMBO J 17(16):4829-36, 8/17/1998. PMCID: PMC1170812.
81. Bradshaw JM, Grucza RA, Ladbury JE, Waksman G. Probing the "two-pronged plug two-holed socket" model for the mechanism of binding of the Src SH2 domain to phosphotyrosyl peptides: a thermodynamic study. Biochemistry 37(25):9083-90, 6/23/1998. PMID: 9636054.
82. O'Brien R, DeDecker B, Fleming KG, Sigler PB, Ladbury JE. The effects of salt on the TATA binding protein-DNA interaction from a hyperthermophilic archaeon. J Mol Biol 279(1):117-25, 5/29/1998. PMID: 9636704.
83. Garret PJ, Ibbett AJ, Ladbury JE, O’Brien R, Hursthouse MB, Malik KMA. Molecular design using electrostatic interactions. 1. Synthesis and properties of flexible tripodand tri- and hexa-cations with restricted conformations. Molecular selection of ferricyanide from ferrocyanide. Tetrahedron 54:949-968, 1998.
84. Haq I, Ladbury JE, Chowdhry BZ, Jenkins TC, Chaires JB. Specific binding of hoechst 33258 to the d(CGCAAATTTGCG)2 duplex: calorimetric and spectroscopic studies. J Mol Biol 271(2):244-57, 8/15/1997. PMID: 9268656.
85. Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW, Pearl LH. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell 90(1):65-75, 7/11/1997. PMID: 9230303.
86. O'Brien R, Wynn R, Driscoll PC, Davis B, Plaxco KW, Sturtevant JM, Ladbury JE. The adaptability of Escherichia coli thioredoxin to non-conservative amino acid substitutions. Protein Sci 6(6):1325-32, 6/1997. PMCID: PMC2143707.
87. Tsai FT, Singh OM, Skarzynski T, Wonacott AJ, Weston S, Tucker A, Pauptit RA, Breeze AL, Poyser JP, O'Brien R, Ladbury JE, Wigley DB. The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin. Proteins 28(1):41-52, 5/1997. PMID: 9144789.
88. Lemmon MA, Bu Z, Ladbury JE, Zhou M, Pinchasi D, Lax I, Engelman DM, Schlessinger J. Two EGF molecules contribute additively to stabilization of the EGFR dimer. EMBO J 16(2):281-94, 1/15/1997. PMCID: PMC1169635.
89. Renzoni DA, Pugh DJ, Siligardi G, Das P, Morton CJ, Rossi C, Waterfield MD, Campbell ID, Ladbury JE. Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase. Biochemistry 35(49):15646-53, 12/10/1996. PMID: 8961927.
90. Tame JR, Sleigh SH, Wilkinson AJ, Ladbury JE. The role of water in sequence-independent ligand binding by an oligopeptide transporter protein. Nat Struct Biol 3(12):998-1001, 12/1996. PMID: 8946852.
91. Morton CJ, Ladbury JE. Water-mediated protein-DNA interactions: the relationship of thermodynamics to structural detail. Protein Sci 5(10):2115-8, 10/1996. PMCID: PMC2143271.
92. Ladbury JE, Hensmann M, Panayotou G, Campbell ID. Alternative modes of tyrosyl phosphopeptide binding to a Src family SH2 domain: implications for regulation of tyrosine kinase activity. Biochemistry 35(34):11062-9, 8/27/1996. PMID: 8780508.
93. Haq I, Ladbury JE, Chowdhry BZ, Jenkins TC. Molecular anchoring of duplex and triplex DNA by disubstituted anthracene-9,10-diones: Calorimetric and spectroscopic studies. Journal of the American Chemical Society 118:10693-10701, 1996.
94. Ladbury JE, Lemmon MA, Zhou M, Green J, Botfield MC, Schlessinger J. Measurement of the binding of tyrosyl phosphopeptides to SH2 domains: a reappraisal. Proc Natl Acad Sci U S A 92(8):3199-203, 4/11/1995. PMCID: PMC42133.
95. Ladbury JE, Wynn R, Thomson JA, Sturtevant JM. Substitution of charged residues into the hydrophobic core of Escherichia coli thioredoxin results in a change in heat capacity of the native protein. Biochemistry 34(7):2148-52, 2/21/1995. PMID: 7857925.
96. Spivak-Kroizman T, Lemmon MA, Dikic I, Ladbury JE, Pinchasi D, Huang J, Jaye M, Crumley G, Schlessinger J, Lax I. Heparin-induced oligomerization of FGF molecules is responsible for FGF receptor dimerization, activation, and cell proliferation. Cell 79(6):1015-24, 12/16/1994. PMID: 7528103.
97. Lemmon MA, Ladbury JE, Mandiyan V, Zhou M, Schlessinger J. Independent binding of peptide ligands to the SH2 and SH3 domains of Grb2. J Biol Chem 269(50):31653-8, 12/16/1994. PMID: 7527391.
98. Ladbury JE, Sturtevant JM, Leontis NB. The thermodynamics of formation of a three-strand, DNA three-way junction complex. Biochemistry 33(22):6828-33, 6/7/1994. PMID: 8204617.
99. Ladbury JE, Wright JG, Sturtevant JM, Sigler PB. A thermodynamic study of the trp repressor-operator interaction. J Mol Biol 238(5):669-81, 5/20/1994. PMID: 8182742.
100. Lemmon MA, Ladbury JE. Thermodynamic studies of tyrosyl-phosphopeptide binding to the SH2 domain of p56lck. Biochemistry 33(17):5070-6, 5/3/1994. PMID: 7513553.
101. Ladbury JE, Kishore N, Hellinga HW, Wynn R, Sturtevant JM. Thermodynamic effects of reduction of the active-site disulfide of Escherichia coli thioredoxin explored by differential scanning calorimetry. Biochemistry 33(12):3688-92, 3/29/1994. PMID: 8142367.
102. Ladbury JE, Wynn R, Hellinga HW, Sturtevant JM. Stability of oxidized Escherichia coli thioredoxin and its dependence on protonation of the aspartic acid residue in the 26 position. Biochemistry 32(29):7526-30, 7/27/1993. PMID: 8393344.
103. Smith GP, Schultz DA, Ladbury JE. A ribonuclease S-peptide antagonist discovered with a bacteriophage display library. Gene 128(1):37-42, 6/15/1993. PMID: 8508958.
104. Hua QX, Ladbury JE, Weiss MA. Dynamics of a monomeric insulin analogue: testing the molten-globule hypothesis. Biochemistry 32(6):1433-42, 2/1993. PMID: 8431423.
105. Ladbury JE, Hu CQ, Sturtevant JM. A differential scanning calorimetric study of the thermal unfolding of mutant forms of phage T4 lysozyme. Biochemistry 31(44):10699-702, 11/10/1992. PMID: 1420185.
106. Ladbury JESD, Currell BR, Horder JR, Parsonage JR, Vidgeon, EA. Applications of the DSC for measurement of thermal conductivity of elastomeric materials. Thermochimica Acta 169:39-45, 1990.

Invited Articles

1. Ladbury JE, Arold ST. Noise in cellular signaling pathways: causes and effects. Trends Biochem Sci 37(5):173-8, 5/2012. e-Pub 2/15/2012. PMCID: PMC3348409.
2. Ladbury JE, Arold ST. Energetics of Src homology domain interactions in receptor tyrosine kinase-mediated signaling. Methods Enzymol 488:147-83, 2011. PMID: 21195228.
3. Ladbury JE. Calorimetry as a tool for understanding biomolecular interactions and an aid to drug design. Biochem Soc Trans 38(4):888-893, 8/2010. PMID: 20658972.
4. Ladbury JE. Measurement of the formation of complexes in tyrosine kinase-mediated signal transduction. Acta Crystallogr D Biol Crystallogr 63(Pt 1):26-31, 1/2007. e-Pub 12/2006. PMCID: PMC2483503.
5. Ababou A, Ladbury JE. Survey of the year 2005: literature on applications of isothermal titration calorimetry. J Mol Recognit 20(1):4-14, Jan-Feb, 1/2007. PMID: 17006876.
6. Ababou A, Ladbury JE. Survey of the year 2004: literature on applications of isothermal titration calorimetry. J Mol Recognit 19(1):79-89, Jan-Feb, 1/2006. PMID: 16220545.
7. Ladbury JE. Application of isothermal titration calorimetry in the biological sciences: things are heating up! Biotechniques 37(6):885-7, 12/2004. PMID: 15597533.
8. Cliff MJ, Gutierrez A, Ladbury JE. A survey of the year 2003 literature on applications of isothermal titration calorimetry. J Mol Recognit 17(6):513-23, Nov-Dec, 11/2004. PMID: 15384176.
9. Ladbury JE, Williams MA. The extended interface: measuring non-local effects in biomolecular interactions. Curr Opin Struct Biol 14(5):562-9, 10/2004. PMID: 15465316.
10. Cliff MJ, Ladbury JE. A survey of the year 2002 literature on applications of isothermal titration calorimetry. J Mol Recognit 16(6):383-91, Nov-Dec, 11/2003. PMID: 14732929.
11. Bergqvist S, Williams MA, O'Brien R, Ladbury JE. Halophilic adaptation of protein-DNA interactions. Biochem Soc Trans 31(Pt 3):677-80, 6/2003. PMID: 12773181.
12. O'Rourke L, Ladbury JE. Specificity is complex and time consuming: mutual exclusivity in tyrosine kinase-mediated signaling. Acc Chem Res 36(6):410-6, 6/2003. PMID: 12809527.
13. Ladbury JE. Isothermal titration calorimetry: Application to structure-based drug design. Thermochimica Acta 380:209-215, 2001.
14. Haq I, Ladbury J. Drug-DNA recognition: energetics and implications for design. J Mol Recognit 13(4):188-97, Jul-Aug, 7/2000. PMID: 10931556.
15. Ladbury JE, Arold S. Searching for specificity in SH domains. Chem Biol 7(1):R3-8, 1/2000. PMID: 10662684.
16. Ladbury JE. Just add water! The effect of water on the specificity of protein-ligand binding sites and its potential application to drug design. Chem Biol 3(12):973-80, 12/1996. PMID: 9000013.
17. Ladbury JE, Chowdhry BZ. Sensing the heat: the application of isothermal titration calorimetry to thermodynamic studies of biomolecular interactions. Chem Biol 3(10):791-801, 10/1996. PMID: 8939696.
18. Ladbury JE. Counting the calories to stay in the groove. Structure 3(7):635-9, 7/1995. PMID: 8591039.
19. Spivak-Kroizman T, Lemmon MA, Dikic I, Ladbury JE, Pinchasi D, Huang J, Jaye M, Crumley G, Schlessinger J, Lax I. How do heparin and heparan-sulfate activate FGF-mitogenic activity. Trends in Glycoscience and Technology 7:447-449, 1995.
20. Ladbury J, Peters R. Turning up the heat on rational drug design. Biotechnology (N Y) 12(11):1083-5, 11/1994. PMID: 7765548.

Editorials

1. Noble M, Ladbury JE. Catalysis and Regulation. Curr Opin Struct Biol 21(6):775-6, 12/2011. PMID: 22142589.

Book Chapters

1. Ladbury JE, Williams MA. Application of isothermal titration calorimetry in exploring the extended interface. In: Protein Reviews. 5. Ed(s) Schuck P. Series Editor Atassi MZ. Kluwer/Plenum Publishing Corporation. New York, USA., 231-254, 2007. ISBN: 10 0-387-35965-6.
2. Ladbury JE. Protein-protein recognition in phosphotyrosine-mediated intracellular signaling. In: Protein Reviews. 3. Ed(s) Waksman G. Series Editor Atassi, MZ. Kluwer/Plenum Publishing Corporation: New York, USA, 165-184, 2005. ISBN: 0-387-24531-6.
3. Thomson JA, Ladbury JE. Isothermal titration calorimetry: A tutorial. In: Biocalorimetry 2: Applications of Calorimetry in the Biological Sciences. Ed(s) Ladbury JE, Doyle ML. John Wiley & Sons Ltd. Chichester, Sussex, UK., 37-58, 2004. ISBN: 0-470-84968-1.
4. Williams MA, Ladbury JE. Hydrogen bonds in protein-ligand interactions. In: Protein-Ligand Interactions: From Molecular Recognition to Drug Design, Methods and Principles in Medicinal Chemistry Series. Ed(s) Böhm H-J, Schneider G. Wiley-VCH. Weinheim, Germany, 137-161, 2003. ISBN: 3-527-30521-1.
5. Panayotou G, Ladbury J. Analysis of SH2 domain--phosphopeptide interactions by isothermal titration calorimetry and surface plasmon resonance. In: Methods Mol Biol. 124, 295-311, 2001. ISBN: 11100483.
6. O’Brien R, Haq I, Ladbury JE. Direct measurement of thermodynamic quantities. In: Drug Receptor Thermodynamics: Introduction and Applications. Ed(s) Raffa RB. John Wiley & Sons Ltd. Chichester, UK., 537-552, 2001. ISBN: 0-471-72042-9.
7. Haq I, O’Brien R, Ladbury JE. General thermodynamic definitions and equations. In: Drug Receptor Thermodynamics: Introduction and Applications. Ed(s) Raffa RB. John Wiley & Sons Ltd. Chichester, UK., 61-82, 2001. ISBN: 0-471-72042-9.
8. O’Brien R, Chowdhry BZ, Ladbury JE. Isothermal titration calorimetry. In: A Practical Approach to Protein-Ligand Interactions. Ed(s) Harding SE, Chowdhry BZ. IRL Press at Oxford University Press: Oxford, UK, 263-286, 2001. ISBN: 0-19-963749-0/6.
9. Schultz DA, Ladbury JE, Smith GP, Fox RO. Interactions of ribonuclease S with ligands from random peptide libraries. In: Biocalorimetry: Applications of Calorimetry to the Biological Sciences. Ed(s) LAdbury JE, Chowdhry BZ. John Wiley & Sons Ltd. Chichester, Sussex, UK, 123-138, 1998. ISBN: 0-471-97781-0.
10. Tame JRH, O’Brien R, Ladbury JE. Isothermal titration calorimetry of biomolecules. In: Biocalorimetry: Applications of Calorimetry to the Biological Sciences. Ed(s) Ladbury JE, Chowdhry BZ. John Wiley & Sons Ltd. Chichester, Sussex, UK, 27-38, 1998. ISBN: 0-471-97781-0.
11. Renzoni DA, Zvelebil MJJM, Lundbäck T,Ladbury JE. Exploring uncharted waters: Water molecules in drug design strategies. In: Structure-based drug design: Strategy, thermodynamics and modeling. Ed(s) Ladbury JE, Connelly PR. R. G. Landes Co./Springer-Verlag: Austin TX. USA/Berlin, Germany, 161-180, 1997. ISBN: 3-540-63250-6.

Books (edited and written)

1. Ladbury JE, Doyle ML. Biocalorimetry II: Applications of Calorimetry in the Study of Biological Systems. John Wiley & Sons Ltd. Chichester, Sussex, UK., 2004. ISBN: 0-470-84968-1.
2. Ladbury JE, Chowdhry BZ. Biocalorimetry: Applications of Calorimetry in the Study of Biological Systems. John Wiley & Sons Ltd. Chichester, Sussex, UK., 1998. ISBN: 0-471-97781-0.
3. Ladbury JE, Connelly PR. Structure-Based Drug Design: Strategy, Thermodynamics and Modelling. R. G. Landes Co/Springer-Verlag: Austin, TX. USA/Berlin, 1997. ISBN: 3-540-63250-6.

Last updated: 7/24/2013