Laurence H Pearl

Summary

Affiliation: Institute of Cancer Research
Country: UK

Publications

  1. ncbi request reprint Hsp90 and Cdc37 -- a chaperone cancer conspiracy
    Laurence H Pearl
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, London, SW3 6JB, UK
    Curr Opin Genet Dev 15:55-61. 2005
  2. doi request reprint The Hsp90 molecular chaperone: an open and shut case for treatment
    Laurence H Pearl
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Biochem J 410:439-53. 2008
  3. ncbi request reprint Structure and mechanism of the Hsp90 molecular chaperone machinery
    Laurence H Pearl
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom
    Annu Rev Biochem 75:271-94. 2006
  4. pmc Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery
    Philippe Meyer
    Chester Beatty Laboratories, Section of Structural Biology, The Institute of Cancer Research, London, UK
    EMBO J 23:1402-10. 2004
  5. pmc Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37
    Cara K Vaughan
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Mol Cell 31:886-95. 2008
  6. pmc Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex
    Rana Dajani
    Section of Structural Biology and Cancer Research UK Centre for Cell and Molecular Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    EMBO J 22:494-501. 2003
  7. pmc Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery
    Philippe Meyer
    Chester Beatty Laboratories, Section of Structural Biology, The Institute of Cancer Research, London, UK
    EMBO J 23:511-9. 2004
  8. ncbi request reprint The Mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37)
    S Mark Roe
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
    Cell 116:87-98. 2004
  9. pmc Structural and functional coupling of Hsp90- and Sgt1-centred multi-protein complexes
    Minghao Zhang
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, London, UK
    EMBO J 27:2789-98. 2008
  10. ncbi request reprint Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex
    Maruf M U Ali
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Nature 440:1013-7. 2006

Detail Information

Publications81

  1. ncbi request reprint Hsp90 and Cdc37 -- a chaperone cancer conspiracy
    Laurence H Pearl
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, London, SW3 6JB, UK
    Curr Opin Genet Dev 15:55-61. 2005
    ..The central role of the Hsp90-Cdc37 chaperone complex makes it an important target for future anti-cancer drug development...
  2. doi request reprint The Hsp90 molecular chaperone: an open and shut case for treatment
    Laurence H Pearl
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Biochem J 410:439-53. 2008
    ..We also identify the gaps in our current understanding and highlight important topics for future research...
  3. ncbi request reprint Structure and mechanism of the Hsp90 molecular chaperone machinery
    Laurence H Pearl
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom
    Annu Rev Biochem 75:271-94. 2006
    ..Additionally, we describe the roles of the plethora of cochaperones with which Hsp90 cooperates and growing insights into their biochemical mechanisms, which come from crystal structures of Hsp90 cochaperone complexes...
  4. pmc Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery
    Philippe Meyer
    Chester Beatty Laboratories, Section of Structural Biology, The Institute of Cancer Research, London, UK
    EMBO J 23:1402-10. 2004
    ....
  5. pmc Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37
    Cara K Vaughan
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Mol Cell 31:886-95. 2008
    ..These data reveal a cyclic regulatory mechanism for Cdc37, in which its constitutive phosphorylation is reversed by targeted dephosphorylation in Hsp90 complexes...
  6. pmc Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex
    Rana Dajani
    Section of Structural Biology and Cancer Research UK Centre for Cell and Molecular Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    EMBO J 22:494-501. 2003
    ..Quantitative analysis suggests that the interaction of GSK3beta with the axin scaffold enhances phosphorylation of beta-catenin by >20 000-fold...
  7. pmc Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery
    Philippe Meyer
    Chester Beatty Laboratories, Section of Structural Biology, The Institute of Cancer Research, London, UK
    EMBO J 23:511-9. 2004
    ....
  8. ncbi request reprint The Mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37)
    S Mark Roe
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
    Cell 116:87-98. 2004
    ..This interaction fixes the lid segment in an open conformation, inserts an arginine side chain into the ATP binding pocket to disable catalysis, and prevents trans-activating interaction of the N domains...
  9. pmc Structural and functional coupling of Hsp90- and Sgt1-centred multi-protein complexes
    Minghao Zhang
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, London, UK
    EMBO J 27:2789-98. 2008
    ....
  10. ncbi request reprint Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex
    Maruf M U Ali
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Nature 440:1013-7. 2006
    ..Contrary to expectations, the closed Hsp90 would not enclose its client proteins but provides a bipartite binding surface whose formation and disruption are coupled to the chaperone ATPase cycle...
  11. pmc Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange
    Antony W Oliver
    Section of Structural Biology, Cancer Research UK DNA Repair Enzymes Group, The Institute of Cancer Research, Chelsea, London, UK
    EMBO J 25:3179-90. 2006
    ..Biochemical data suggest that this dimer is the biologically active state promoted by ATM-phosphorylation, and also suggests a mechanism for dimerisation-driven activation of Chk2 by trans-phosphorylation...
  12. pmc Structural and functional analysis of the Crb2-BRCT2 domain reveals distinct roles in checkpoint signaling and DNA damage repair
    Mairi L Kilkenny
    CR UK DNA Repair Enzymes Group, Section of Structural Biology, The Institute of Cancer Research, Chelsea, London SW3 6JB, United Kingdon
    Genes Dev 22:2034-47. 2008
    ..However, disrupting phosphopeptide binding slows formation of ssDNA-binding protein (Rpa1/Rad11) foci and reduces levels of Rad22(Rad52) recombination foci, indicating a DNA repair defect...
  13. ncbi request reprint Structure of an Hsp90-Cdc37-Cdk4 complex
    Cara K Vaughan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, UK
    Mol Cell 23:697-707. 2006
    ..Comparison with the crystal structure of Hsp90 allows us to identify the locations of Cdc37 and Cdk4 in the complex and suggests a mechanism by which conformational changes in the kinase are coupled to the Hsp90 ATPase cycle...
  14. doi request reprint Structural insights into formation of an active signaling complex between Rac and phospholipase C gamma 2
    Tom D Bunney
    Section of Cell and Molecular Biology, The Institute of Cancer Research, London, UK
    Mol Cell 34:223-33. 2009
    ....
  15. pmc Structural basis for assembly of Hsp90-Sgt1-CHORD protein complexes: implications for chaperoning of NLR innate immunity receptors
    Minghao Zhang
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Mol Cell 39:269-81. 2010
    ....
  16. ncbi request reprint Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions
    Philippe Meyer
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, SW3 6JB, London, United Kingdom
    Mol Cell 11:647-58. 2003
    ....
  17. pmc A common conformationally coupled ATPase mechanism for yeast and human cytoplasmic HSP90s
    Cara K Vaughan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, London, UK
    FEBS J 276:199-209. 2009
    ....
  18. doi request reprint Crystal structure of the rad9-rad1-hus1 DNA damage checkpoint complex--implications for clamp loading and regulation
    Andrew S Doré
    CR UK DNA Repair Enzymes Group, Section of Structural Biology, The Institute of Cancer Research, 237 Fulham Road, Chelsea, SW36JB London, UK
    Mol Cell 34:735-45. 2009
    ..Biochemical analysis reveals a single repair enzyme-binding site on 9-1-1 that can be blocked competitively by the PCNA-binding cell-cycle regulator p21(cip1/waf1)...
  19. doi request reprint CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors
    Victoria E Anderson
    Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Cancer Res 71:463-72. 2011
    ..Consequently, our findings imply that CHK2 inhibitors may exert therapeutic activity in combination with PARP inhibitors...
  20. pmc Structural basis for recruitment of BRCA2 by PALB2
    Antony W Oliver
    Cancer Research UK DNA Repair Enzymes Group, Section of Structural Biology, 237 Fulham Road, London SW3 6JB, UK
    EMBO Rep 10:990-6. 2009
    ..The structure shows the molecular determinants of this important protein-protein interaction and explains the effects of both cancer-associated truncating mutants in PALB2 and missense mutations in the amino-terminal region of BRCA2...
  21. pmc Specific recognition of a multiply phosphorylated motif in the DNA repair scaffold XRCC1 by the FHA domain of human PNK
    Ammar A E Ali
    Cancer Research UK DNA Repair Enzyme Group, Section of Structural Biology, The Institute of Cancer Research, London SW3 6JB, UK
    Nucleic Acids Res 37:1701-12. 2009
    ..The high-resolution crystal structure of a PNK-FHA-XRCC1 phosphopeptide complex reveals the basis for this unusual bis-phosphopeptide recognition, which is probably a common feature of the known XRCC1-associating end-processing enzymes...
  22. ncbi request reprint The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors
    Kwai Ming J Cheung
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Cancer Research UK and Haddow Laboratories, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Bioorg Med Chem Lett 15:3338-43. 2005
    ..Some initial structure-activity relationships are discussed, as well as the crystal structure of CCT018159 bound to Hsp90...
  23. ncbi request reprint Crystal structure of the retinoblastoma protein N domain provides insight into tumor suppression, ligand interaction, and holoprotein architecture
    Markus Hassler
    Cancer Research UK Centre for Cell and Molecular Biology, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    Mol Cell 28:371-85. 2007
    ..Additionally, this analysis suggests a coherent conformation for the Rb holoprotein in which RbN and pocket domains directly interact, and which can be modulated through ligand binding and possibly Rb phosphorylation...
  24. pmc Insights into histone code syntax from structural and biochemical studies of CARM1 methyltransferase
    Wyatt W Yue
    Cancer Research UK DNA Repair Enzyme Research Group, Section of Structural Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, UK
    EMBO J 26:4402-12. 2007
    ..Together with the absence of specificity subsites in the structure, this suggests an electrostatic sensing mechanism for communicating the modification status of vicinal residues as part of the syntax of the 'histone code.'..
  25. ncbi request reprint Structure and specificity of the vertebrate anti-mutator uracil-DNA glycosylase SMUG1
    Jane E A Wibley
    Cancer Research UK DNA Repair Enzyme Group, Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
    Mol Cell 11:1647-59. 2003
    ..This structure indicates a more invasive interaction with dsDNA than observed with other UDGs and reveals an elegant water displacement/replacement mechanism that allows SMUG1 to exclude thymine from its active site while accepting HmU...
  26. doi request reprint A combinatorial method to enable detailed investigation of protein-protein interactions
    Kate Maclagan
    The Institute of Structural and Molecular Biology, Research Department of Structural and Molecular Biology, University College London, Gower Street, London, WC1E 6BT, UK
    Future Med Chem 3:271-82. 2011
    ..However, attempting the discovery of stable core complexes using informed trial-and-error approaches can prove time and resource intensive...
  27. pmc Evidence for a remodelling of DNA-PK upon autophosphorylation from electron microscopy studies
    Edward P Morris
    Structural Electron Microscopy Group, Section of Structural Biology, The Institute of Cancer Research, London SW3 6JB, UK
    Nucleic Acids Res 39:5757-67. 2011
    ..Together, our data indicate a substantial remodelling of DNA-PK holo-enzyme upon autophosphorylation, which is crucial to the release of protein factors from a repaired DNA double-strand break...
  28. doi request reprint Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2
    John J Caldwell
    Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    J Med Chem 54:580-90. 2011
    ..In addition to showing mechanistic inhibition of CHK2 in HT29 human colon cancer cells, a concentration dependent radioprotective effect in mouse thymocytes was demonstrated for the potent inhibitor 46 (CCT241533)...
  29. ncbi request reprint Activation segment exchange: a common mechanism of kinase autophosphorylation?
    Antony W Oliver
    Cancer Research UK DNA Repair Enzymes Group, Section of Structural Biology, The Institute of Cancer Research, Chelsea, London, SW3 6JB, UK
    Trends Biochem Sci 32:351-6. 2007
    ....
  30. pmc Crystal structure of the proximal BAH domain of the polybromo protein
    Antony W Oliver
    CR UK DNA Repair Enzymes Group, Section of Structural Biology, The Institute of Cancer Research, 237 Fulham Road, Chelsea, London SW3 6JB, UK
    Biochem J 389:657-64. 2005
    ..6 A (1 A=0.1 nm). Structure-based sequence analysis reveals several features that may be involved in mediating protein-protein interactions...
  31. pmc Structure of an archaeal PCNA1-PCNA2-FEN1 complex: elucidating PCNA subunit and client enzyme specificity
    Andrew S Doré
    CR UK DNA Repair Enzymes Group, Section of Structural Biology, The Institute of Cancer Research, 237 Fulham Road, Chelsea, London, SW3 6JB, UK
    Nucleic Acids Res 34:4515-26. 2006
    ....
  32. pmc A novel expression system of domain I of human beta2 glycoprotein I in Escherichia coli
    Yiannis Ioannou
    Centre for Rheumatology, Department of Medicine, University College London, Arthur Stanley House, 40 50 Tottenham Street, London, W1T 4NJ, UK
    BMC Biotechnol 6:8. 2006
    ..Expressing this protein in bacteria could facilitate studies investigating how this molecule interacts with aPL...
  33. ncbi request reprint Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex
    Minghao Zhang
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
    Mol Cell 20:525-38. 2005
    ....
  34. pmc Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2
    Antony W Oliver
    Cancer Research UK DNA Repair Enzyme Group, Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Nucleic Acids Res 32:456-64. 2004
    ..8 A resolution, and compare this to the catalytic fragment of PARP-1, with an emphasis on providing a possible framework for rational drug design in order to develop future isoform-specific inhibitors...
  35. pmc Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1
    Mathieu Rappas
    Cancer Research UK DNA Repair Enzyme Group, Section of Structural Biology, The Institute of Cancer Research, London, UK
    Nucleic Acids Res 39:313-24. 2011
    ..We show that the site in the second but not third BRCT domain in the N-terminus of TopBP1, provides specific interaction with a phosphorylated motif at pSer387 in Rad9, which can be generated by CK2...
  36. ncbi request reprint Structural and mechanistic insights into ras association domains of phospholipase C epsilon
    Tom D Bunney
    Cancer Research UK Centre for Cell and Molecular Biology, Chester Beatty Laboratories, The Institute of Cancer Research, Fulham Road, London SW3 6JB, United Kingdom
    Mol Cell 21:495-507. 2006
    ..Studies of PLCepsilon regulation suggest that, in a cellular context, the RA2 domain, in a mode specific to PLCepsilon, has a role in membrane targeting with further regulatory impact on PLC activity...
  37. doi request reprint Structural basis of the radicicol resistance displayed by a fungal hsp90
    Chrisostomos Prodromou
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, U K
    ACS Chem Biol 4:289-97. 2009
    ..To the best of our knowledge, this is the first demonstration that it is possible for Hsp90 inhibitor resistance to arise by subtle alteration to the structure of Hsp90 itself...
  38. doi request reprint Identification and characterisation of 2-aminopyridine inhibitors of checkpoint kinase 2
    Stephen Hilton
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Bioorg Med Chem 18:707-18. 2010
    ..Compounds from this series showed activity in cell-based mechanistic assays for inhibition of CHK2...
  39. pmc Structural basis for recruitment of translesion DNA polymerase Pol IV/DinB to the beta-clamp
    Karen A Bunting
    The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    EMBO J 22:5883-92. 2003
    ....
  40. pmc Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response
    Maruf M U Ali
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, London, UK
    EMBO J 30:894-905. 2011
    ..These studies identify human Ire1α as a target for development of ATP-competitive inhibitors that will modulate the UPR in human cells, which has particular relevance for myeloma and other secretory malignancies...
  41. ncbi request reprint Three-dimensional structure of the human DNA-PKcs/Ku70/Ku80 complex assembled on DNA and its implications for DNA DSB repair
    Laura Spagnolo
    Section of Structural Biology and Cancer Research UK DNA Repair Enzyme Research Group, Institute of Cancer Research, Chester Beatty Laboratories, London
    Mol Cell 22:511-9. 2006
    ....
  42. pmc Visualization of a DNA-PK/PARP1 complex
    Laura Spagnolo
    Cancer Research UK DNA Repair Enzymes Group, The Institute of Cancer Research, London SW3 6JB, UK
    Nucleic Acids Res 40:4168-77. 2012
    ..We also propose a NHEJ model where protein-protein interactions alter substantially the architecture of DNA-PK dimers at DSBs, to trigger subsequent interactions or enzymatic reactions...
  43. pmc The crystal structure of yeast CCT reveals intrinsic asymmetry of eukaryotic cytosolic chaperonins
    Carien Dekker
    Section of Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, UK
    EMBO J 30:3078-90. 2011
    ..The location of the evolutionarily conserved N-terminus of Cct5 on the outside of the barrel, confirmed by mutational studies, is unique to eukaryotic cytosolic chaperonins...
  44. pmc Crystal structure of the Escherichia coli dcm very-short-patch DNA repair endonuclease bound to its reaction product-site in a DNA superhelix
    Karen A Bunting
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Nucleic Acids Res 31:1633-9. 2003
    ..The structure reveals the presence of a Hoogsteen base pair within the deaminated recognition sequence and the substantial distortions of the DNA that accompany Vsr binding to product sites...
  45. ncbi request reprint Structure and functional relationships of Hsp90
    Chrisostomos Prodromou
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Curr Cancer Drug Targets 3:301-23. 2003
    ..The structure of the middle region of Hsp90 will also accelerate our understanding of client protein interactions since this region is implicated in their recognition and in particular their active-site openings...
  46. pmc The ATPase-dependent chaperoning activity of Hsp90a regulates thick filament formation and integration during skeletal muscle myofibrillogenesis
    Thomas A Hawkins
    Department of Anatomy and Developmental Biology, UCL, London, UK
    Development 135:1147-56. 2008
    ..Our studies reveal a surprisingly specific developmental role for a single Hsp90 gene in a regulatory pathway controlling late steps in sarcomere assembly...
  47. ncbi request reprint Regulation of protein kinases in insulin, growth factor and Wnt signalling
    Laurence H Pearl
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Curr Opin Struct Biol 12:761-7. 2002
    ..Structural studies of GSK3beta complexes are contributing to our understanding of the phosphorylation-independent mechanism that insulates the Wnt and insulin/growth factor pathways...
  48. ncbi request reprint High-throughput screening assay for inhibitors of heat-shock protein 90 ATPase activity
    Martin G Rowlands
    Cancer Research UK Centre for Cancer Therapeutics, Haddow Laboratories, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
    Anal Biochem 327:176-83. 2004
    ..The assay was robust and reproducible (2-8% CV) and used to screen a compound collection of approximately 56,000 compounds in 384-well format with Z' factors between 0.6 and 0.8...
  49. ncbi request reprint Crystal structure of the C-terminal WD40 repeat domain of the human Groucho/TLE1 transcriptional corepressor
    Laura M Pickles
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, SW3 6JB, London, United Kingdom
    Structure 10:751-61. 2002
    ..Analysis of missense mutations in the C. elegans Groucho homolog UNC-37 identifies sites of interaction with repression effectors, and suggests an induced fit binding site for eh1 domains of Engrailed-type transcription factors...
  50. pmc MoKCa database--mutations of kinases in cancer
    Christopher J Richardson
    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Nucleic Acids Res 37:D824-31. 2009
    ....
  51. pmc Lupus autoantibodies to native DNA preferentially bind DNA presented on PolIV
    Sanjeev Kumar
    Centre for Rheumatology, Department of Medicine, University College London Hospital, London, UK
    Immunology 114:418-27. 2005
    ..This difference in binding ability may help to distinguish those dsDNA antibodies that are more pathogenic...
  52. ncbi request reprint Crystal structure of the CCTgamma apical domain: implications for substrate binding to the eukaryotic cytosolic chaperonin
    Günter Pappenberger
    Section of Structural Biology, The Institute of Cancer Research, London, UK
    J Mol Biol 318:1367-79. 2002
    ..The site and nature of substrate interaction are thus profoundly different between CCT and its eubacterial homologue GroEL, consistent with their different functions in general versus specific protein folding assistance...
  53. ncbi request reprint An iron-sulfur cluster in the family 4 uracil-DNA glycosylases
    John A Hinks
    Cancer Research UK DNA Repair Enzyme Group, Section of Structural Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, United Kingdom
    J Biol Chem 277:16936-40. 2002
    ..Similar to the Nth/MutY enzymes, the Family 4 UDG centers probably play a structural rather than a catalytic role...
  54. pmc Cyclin-cyclin-dependent kinase regulatory response is linked to substrate recognition
    Maria Emanuela Cuomo
    Section of Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, SW3 6JB London, United Kingdom
    J Biol Chem 286:9713-25. 2011
    ..Together our work provides novel insight into the molecular mechanisms governing cyclin-CDK function and regulation and defines the biological forces that may have driven evolution of viral cyclins...
  55. ncbi request reprint Identification of the Axin and Frat binding region of glycogen synthase kinase-3
    Elizabeth Fraser
    Cancer Research Campaign Centre for Cell and Molecular Biology and Section of Structural Biology, Institute of Cancer Research, 237 Fulham Rd, London SW3 6JB, United Kingdom
    J Biol Chem 277:2176-85. 2002
    ..Surprisingly, we find no genetic interaction between a non-Axin-binding GSK-3 mutant and T-cell factor activity, arguing that Axin interactions alone cannot explain the regulation of T-cell factor-mediated gene expression...
  56. ncbi request reprint Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone aha1
    Barry Panaretou
    Division of Life Sciences, Franklin Wilkins Building, 150 Stamford Street, SE1 9NN, London, United Kingdom
    Mol Cell 10:1307-18. 2002
    ..The identification of these Hsp90 cochaperone activators adds to the complex roles of cochaperones in regulating the ATPase-coupled conformational changes of the Hsp90 chaperone cycle...
  57. pmc Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs
    Angel Rivera-Calzada
    Centro de Investigaciones Biologicas CIB, Spanish National Research Council CSIC, Ramiro de Maeztu 9, Campus Complutense University, Madrid 28040, Spain
    EMBO Rep 8:56-62. 2007
    ....
  58. ncbi request reprint Electron microscopy studies on DNA recognition by DNA-PK
    Oscar Llorca
    Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas CSIC, Ramiro de Maeztu 9, Campus Universidad Complutense, Madrid 28040, Spain
    Micron 35:625-33. 2004
    ..Several studies have made use of the electron microscope to reveal the three-dimensional architecture of DNA-PK and the structural basis for the recognition of damaged DNA and the activation of DNA-PK's kinase activity...
  59. ncbi request reprint The 3D solution structure of the C-terminal region of Ku86 (Ku86CTR)
    Richard Harris
    Bloomsbury Centre for Structural Biology, University College London, Gower Street, London WC1E 6BT, UK
    J Mol Biol 335:573-82. 2004
    ..Two prominent hydrophobic pockets in the gap between helices alpha2 and alpha4 suggest a potential ligand-binding characteristic for this globular domain...
  60. pmc Visualization of DNA-induced conformational changes in the DNA repair kinase DNA-PKcs
    Jasminka Boskovic
    Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, Ramiro de Maeztu 9, Campus Universidad Complutense, 28040 Madrid, Spain
    EMBO J 22:5875-82. 2003
    ..We suggest that the observed domain movements might help the binding and maintenance of DNA-PKcs' interaction with DNA at the sites of damage, and that these conformational changes activate the kinase...
  61. ncbi request reprint Crystal structure of alanine:glyoxylate aminotransferase and the relationship between genotype and enzymatic phenotype in primary hyperoxaluria type 1
    Xiaoxuan Zhang
    Department of Biology, University College London, Gower Street, London WC1E 6BT, UK
    J Mol Biol 331:643-52. 2003
    ....
  62. ncbi request reprint Structural basis for uracil recognition by archaeal family B DNA polymerases
    Mark J Fogg
    School of Cell and Molecular Biosciences, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
    Nat Struct Biol 9:922-7. 2002
    ....
  63. ncbi request reprint Backbone 1H, 13C, and 15N resonance assignments for the C-terminal region of Ku86 (Ku86CTR)
    Richard Harris
    J Biomol NMR 22:373-4. 2002
  64. ncbi request reprint Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37
    Giuliano Siligardi
    Pharmaceutical Optical Spectroscopy Centre, Department of Pharmacy, The Division of Life Sciences, King s College London, United Kingdom
    J Biol Chem 277:20151-9. 2002
    ..However, unlike Sti1/Hop/p60, which can displace geldanamycin upon binding to Hsp90, Cdc37p/p50(cdc37) forms a stable complex with geldanamycin-bound Hsp90 and may be sequestered in geldanamycin-inhibited Hsp90 complexes in vivo...
  65. ncbi request reprint Co-chaperone regulation of conformational switching in the Hsp90 ATPase cycle
    Giuliano Siligardi
    Pharmaceutical Optical Spectroscopy Centre and Division of Life Sciences, Department of Pharmacy, King s College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NN, United Kingdom
    J Biol Chem 279:51989-98. 2004
    ..These data indicated that Sba1 and Aha1 regulate Hsp90 by influencing the conformational state of the "ATP lid" and consequent N-terminal dimerization, whereas Sti1 does not...
  66. ncbi request reprint Three-dimensional structure and regulation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs)
    Angel Rivera-Calzada
    Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas CSIC, Ramiro de Maeztu 9, Campus Universidad Complutense, 28040 Madrid, Spain
    Structure 13:243-55. 2005
    ..Comparison of DNA-PKcs with another PIKK DNA repair factor, ATM, defines a common architecture for this important protein family...
  67. ncbi request reprint Reciprocal "flipping" underlies substrate recognition and catalytic activation by the human 8-oxo-guanine DNA glycosylase
    Magnar Bjørås
    Department of Molecular Biology, Institute of Medical Microbiology, University of Oslo, The National Hospital, Norway
    J Mol Biol 317:171-7. 2002
    ..It has been possible to identify a mechanism whereby the catalytic residue Lys 249 is "primed" for nucleophilic attack of the N-glycosidic bond...
  68. ncbi request reprint Qri2/Nse4, a component of the essential Smc5/6 DNA repair complex
    Bin Hu
    Department of Life Sciences, King s College London, London SE1 9NN, UK
    Mol Microbiol 55:1735-50. 2005
    ..This could imply a role for Nse4 in maintenance of higher order chromosome structure...
  69. ncbi request reprint Molecular recognition of transcriptional repressor motifs by the WD domain of the Groucho/TLE corepressor
    Barbara H Jennings
    Developmental Genetics Laboratory, Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Mol Cell 22:645-55. 2006
    ..Our structural and functional analysis explains the rigid conservation of the WRPW motif, the sequence flexibility of eh1 motifs, and other aspects of repressor recognition by Gro in vivo...
  70. pmc Activation segment dimerization: a mechanism for kinase autophosphorylation of non-consensus sites
    Ashley C W Pike
    Structural Genomics Consortium, Botnar Research Centre, University of Oxford, Oxford, UK
    EMBO J 27:704-14. 2008
    ..Based on the presented structural and functional data, a model for specific activation segment phosphorylation at non-consensus substrate sites is proposed that is likely to be common to other kinases from diverse subfamilies...
  71. ncbi request reprint 4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer
    Paul A Brough
    Vernalis Ltd, Granta Park, Great Abington, Cambridge CB21 6GB, U K p brough vernalis com
    J Med Chem 51:196-218. 2008
    ..Compound 40f is retained in tumors in vivo when administered i.p., as evaluated by cassette dosing in tumor-bearing mice. In a human colon cancer xenograft model, 40f inhibits tumor growth by approximately 50%...
  72. ncbi request reprint Backbone resonance assignments of the 25kD N-terminal ATPase domain from the Hsp90 chaperone
    Reza M Salek
    J Biomol NMR 23:327-8. 2002
  73. ncbi request reprint Inhibition of Hsp90 with synthetic macrolactones: synthesis and structural and biological evaluation of ring and conformational analogs of radicicol
    Nicolas Proisy
    School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom
    Chem Biol 13:1203-15. 2006
    ..e., depletion of client proteins with upregulation of Hsp70...
  74. pmc Combinatorial Domain Hunting: An effective approach for the identification of soluble protein domains adaptable to high-throughput applications
    Stefanie Reich
    School of Crystallography, Birkbeck College, London WC1E 7HX, United Kingdom
    Protein Sci 15:2356-65. 2006
    ..As a proof of principle, we applied CDH to p85alpha, successfully identifying soluble and highly expressed constructs encapsulating all the known globular domains, and immediately suitable for downstream applications...
  75. pmc Chaperone ligand-discrimination by the TPR-domain protein Tah1
    Stefan H Millson
    Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK
    Biochem J 413:261-8. 2008
    ..In the present study we also show that Tah1 can affect the ATPase activity of Hsp90, in common with some other TPR-domain proteins...
  76. ncbi request reprint Anti-cardiolipin/beta-2 glycoprotein activities co-exist on human anti-DNA antibody light chains
    Sanjeev Kumar
    Bloomsbury Rheumatology Unit, Department of Medicine, Centre for Rheumatology, University College London Hospital, Arthur Stanley House, 40 50 Tottenham Street, London W1P 9PG, UK
    Mol Immunol 40:517-30. 2003
    ..Computer-generated models of the three-dimensional structures of the auto-antibodies and their hybrids, suggest predominant interaction of their light chains with domain IV of beta2-GPI...
  77. pmc Expressed in the yeast Saccharomyces cerevisiae, human ERK5 is a client of the Hsp90 chaperone that complements loss of the Slt2p (Mpk1p) cell integrity stress-activated protein kinase
    Andrew W Truman
    Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, United Kingdom
    Eukaryot Cell 5:1914-24. 2006
    ..Complementation of the slt2Delta yeast defect by ERK5 expression establishes a new tool with which to screen for novel agonists and antagonists of ERK5 signaling as well as for isolating mutant forms of ERK5...
  78. ncbi request reprint Sensitivity to Hsp90-targeting drugs can arise with mutation to the Hsp90 chaperone, cochaperones and plasma membrane ATP binding cassette transporters of yeast
    Peter W Piper
    Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield, UK
    Eur J Biochem 270:4689-95. 2003
    ..It is shown that these mutations render at least one Hsp90-dependent process (deactivation of heat-induced heat shock factor activity) more sensitive to drug inhibition in vivo...
  79. pmc Investigating the protein-protein interactions of the yeast Hsp90 chaperone system by two-hybrid analysis: potential uses and limitations of this approach
    Stefan H Millson
    Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK
    Cell Stress Chaperones 9:359-68. 2004
    ..A number of potentially novel cochaperone interactions were also identified, providing a framework for these to be analyzed further using other techniques...
  80. pmc A two-hybrid screen of the yeast proteome for Hsp90 interactors uncovers a novel Hsp90 chaperone requirement in the activity of a stress-activated mitogen-activated protein kinase, Slt2p (Mpk1p)
    Stefan H Millson
    Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, United Kingdom
    Eukaryot Cell 4:849-60. 2005
    ..The interaction between Hsp90 and (Y-P,T-P)Slt2p, characterized in this study, is probably essential in this Hsp90 facilitation of the Rlm1p activation by Slt2p...
  81. ncbi request reprint Beta-2-glycoprotein specificity of human anti-phospholipid antibody resides on the light chain: a novel mechanism for acquisition of cross-reactivity by an autoantibody
    Sanjeev Kumar
    Department of Medicine, Centre for Rheumatology, Bloomsbury Rheumatology Unit, University College London Hospital, Arthur Stanley House, 40 50 Tottenham Street, London W1P 9PG, UK
    Mol Immunol 42:39-48. 2005
    ..The possible mechanisms that such antibodies may employ to recognise their antigens, are discussed...