Cellular and Molecular Life Sciences

, Volume 69, Issue 2, pp 283–297 | Cite as

Anopheles gambiae odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents

  • K. E. Tsitsanou
  • T. Thireou
  • C. E. Drakou
  • K. Koussis
  • M. V. Keramioti
  • D. D. Leonidas
  • E. Eliopoulos
  • K. Iatrou
  • S. E. Zographos
Research article

Abstract

Insect odorant binding proteins (OBPs) are the first components of the olfactory system to encounter and bind attractant and repellent odors emanating from various sources for presentation to olfactory receptors, which trigger relevant signal transduction cascades culminating in specific physiological and behavioral responses. For disease vectors, particularly hematophagous mosquitoes, repellents represent important defenses against parasitic diseases because they effect a reduction in the rate of contact between the vectors and humans. OBPs are targets for structure-based rational approaches for the discovery of new repellent or other olfaction inhibitory compounds with desirable features. Thus, a study was conducted to characterize the high resolution crystal structure of an OBP of Anopheles gambiae, the African malaria mosquito vector, in complex with N,N-diethyl-m-toluamide (DEET), one of the most effective repellents that has been in worldwide use for six decades. We found that DEET binds at the edge of a long hydrophobic tunnel by exploiting numerous non-polar interactions and one hydrogen bond, which is perceived to be critical for DEET’s recognition. Based on the experimentally determined affinity of AgamOBP1 for DEET (Kd of 31.3 μΜ) and our structural data, we modeled the interactions for this protein with 29 promising leads reported in the literature to have significant repellent activities, and carried out fluorescence binding studies with four highly ranked ligands. Our experimental results confirmed the modeling predictions indicating that structure-based modeling could facilitate the design of novel repellents with enhanced binding affinity and selectivity.

Keywords

Crystal structure Molecular modeling AgamOBP1 DEET Malaria 

Abbreviations

AgamOBP1

Odorant binding protein 1 from Anopheles gambiae

OR

Odorant receptor

ON

Olfactory neuron

DEET

N,N-Diethyl-m-toluamide

1-NPN

N-Phenyl-1-naphthylamine

IPTG

Isopropyl-galacto-pyranoside

MOP

(5R,6S)-6-Acetoxy-5-hexadecanolide

TLS

Translation/libration/screw

vdW

van der Waals

Supplementary material

18_2011_745_MOESM1_ESM.pdf (744 kb)
Supplementary material 1 (PDF 743 kb)

References

  1. 1.
    World Health Organization (2010) Malaria fact sheet N. 94. WHO website (online). http://www.who.int/mediacentre/factsheets/fs094/en/
  2. 2.
    Kar S, Kar S (2010) Control of malaria. Nat Rev Drug Discov 9(7):511–512. doi:10.1038/Nrd3207 PubMedCrossRefGoogle Scholar
  3. 3.
    Gershon D (2002) Malaria research tools up for the future. Nature 419(6906):4–5. doi:10.1038/nj6906-04a PubMedCrossRefGoogle Scholar
  4. 4.
    Ito J, Ghosh A, Moreira LA, Wimmer EA, Jacobs-Lorena M (2002) Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite. Nature 417(6887):452–455. doi:10.1038/417452a PubMedCrossRefGoogle Scholar
  5. 5.
    Kim W, Koo H, Richman AM, Seeley D, Vizioli J, Klocko AD, O’Brochta DA (2004) Ectopic expression of a cecropin transgene in the human malaria vector mosquito Anopheles gambiae (Diptera: Culicidae): effects on susceptibility to Plasmodium. J Med Entomol 41(3):447–455PubMedCrossRefGoogle Scholar
  6. 6.
    Eskenazi B, Chevrier J, Rosas LG, Anderson HA, Bornman MS, Bouwman H, Chen AM, Cohn BA, de Jager C, Henshel DS, Leipzig F, Leipzig JS, Lorenz EC, Snedeker SM, Stapleton D (2009) The Pine river statement: human health consequences of DDT use. Environ Health Perspect 117(9):1359–1367. doi:10.1289/Ehp.11748 PubMedGoogle Scholar
  7. 7.
    van den Berg H (2009) Global status of DDT and its alternatives for use in vector control to prevent disease. Environ Health Perspect 117(11):1656–1663. doi:10.1289/Ehp.0900785 PubMedCrossRefGoogle Scholar
  8. 8.
    Ranson H, Abdallah H, Badolo A, Guelbeogo WM, Kerah-Hinzoumbe C, Yangalbe-Kalnone E, Sagnon N, Simard F, Coetzee M (2009) Insecticide resistance in Anopheles gambiae: data from the first year of a multi-country study highlight the extent of the problem. Malaria J 8:299. doi:10.1186/1475-2875-8-299 CrossRefGoogle Scholar
  9. 9.
    Moore SJ, Debboun M (2007). In: Debboun M, Frances SP, Strickman D (eds) Insect repellents: principles, methods, and uses. CRC Press, Boca Raton, pp 3–30Google Scholar
  10. 10.
    Mccabe ET, Barthel WF, Gertler SI, Hall SA (1954) Insect repellents. 3. N,N-diethylamides. J Org Chem 19(4):493–498CrossRefGoogle Scholar
  11. 11.
    Frances SP, Cooper RD, Popat S, Beebe NW (2001) Field evaluation of repellents containing DEET and AI3-37220 against Anopheles koliensis in Papua New Guinea. J Am Mosq Control Assoc 17(1):42–44PubMedGoogle Scholar
  12. 12.
    Xue RD, Ali A, Barnard DR (2003) Laboratory evaluation of toxicity of 16 insect repellents in aerosol sprays to adult mosquitoes. J Am Mosq Control Assoc 19(3):271–274PubMedGoogle Scholar
  13. 13.
    Bohbot JD, Dickens JC (2010) Insect repellents: modulators of mosquito odorant receptor activity. PLoS ONE 5(8):e12138. doi:10.1371/journal.pone.0012138 PubMedCrossRefGoogle Scholar
  14. 14.
    Dogan EB, Ayres JW, Rossignol PA (1999) Behavioural mode of action of DEET: inhibition of lactic acid attraction. Med Vet Entomol 13(1):97–100PubMedCrossRefGoogle Scholar
  15. 15.
    Ditzen M, Pellegrino M, Vosshall LB (2008) Insect odorant receptors are molecular targets of the insect repellent DEET. Science 319(5871):1838–1842. doi:10.1126/science.1153121 PubMedCrossRefGoogle Scholar
  16. 16.
    Syed Z, Leal WS (2008) Mosquitoes smell and avoid the insect repellent DEET. Proc Natl Acad Sci USA 105(36):13598–13603. doi:10.1073/pnas.0805312105 PubMedCrossRefGoogle Scholar
  17. 17.
    Robbins PJ, Cherniack MG (1986) Review of the biodistribution and toxicity of the insect repellent N,N-diethyl-m-toluamide (DEET). J Toxicol Environ Health 18(4):503–525PubMedCrossRefGoogle Scholar
  18. 18.
    Corbel V, Stankiewicz M, Pennetier C, Fournier D, Stojan J, Girard E, Dimitrov M, Molgo J, Hougard JM, Lapied B (2009) Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent DEET. BMC Biol 7:47. doi:10.1186/1741-7007-7-47
  19. 19.
    Rutledge LC, Moussa MA, Lowe CA, Sofield RK (1978) Comparative sensitivity of mosquito species and strains to repellent diethyl toluamide. J Med Entomol 14(5):536–541PubMedGoogle Scholar
  20. 20.
    Boeckh J, Breer H, Geier M, Hoever FP, Kruger BW, Nentwig G, Sass H (1996) Acylated 1, 3-aminopropanols as repellents against bloodsucking arthropods. Pest Sci 48(4):359–373CrossRefGoogle Scholar
  21. 21.
    Boeckh J, Hoever FP, Kruger BW, Nentwig G, Roder K (1996) N-acylated 2-(2-hydroxyethyl)-piperidines—a new class of insect and tick repellents. Abstr Pap Am Chem Soc 212:20 (Agro)Google Scholar
  22. 22.
    Astroff AB, Freshwater KJ, Young AD, Stuart BP, Sangha GK, Thyssen JH (1999) The conduct of a two-generation reproductive toxicity study via dermal exposure in the Sprague-Dawley rat—a case study with KBR 3023 (a prospective insect repellent). Reprod Toxicol 13(3):223–232PubMedCrossRefGoogle Scholar
  23. 23.
    Natarajan R, Basak SC, Balaban AT, Klun JA, Schmidt WF (2005) Chirality index, molecular overlay and biological activity of diastereoisomeric mosquito repellents. Pest Manag Sci 61(12):1193–1201PubMedCrossRefGoogle Scholar
  24. 24.
    Gaudin JM, Lander T, Nikolaenko O (2008) Carboxamides combining favorable olfactory properties with insect repellency. Chem Biodivers 5(4):617–635. doi:10.1002/cbdv.200890058 PubMedCrossRefGoogle Scholar
  25. 25.
    Pridgeon JW, Becnel JJ, Bernier UR, Clark GG, Linthicum KJ (2010) Structure-activity relationships of 33 carboxamides as toxicants against female Aedes aegypti (Diptera: Culicidae). J Med Entomol 47(2):172–178. doi:10.1603/Me08265 PubMedCrossRefGoogle Scholar
  26. 26.
    Katritzky AR, Wang ZQ, Slavon S, Dobchev DA, Hall CD, Tsikolia M, Bernier UR, Elejalde NM, Clark GG, Linthicum KJ (2010) Novel carboxamides as potential mosquito repellents. J Med Entomol 47(5):924–938. doi:10.1603/Me09284 PubMedCrossRefGoogle Scholar
  27. 27.
    Katritzky AR, Wang ZQ, Slavov S, Tsikolia M, Dobchev D, Akhmedov NG, Hall CD, Bernier UR, Clark GG, Linthicum KJ (2008) Synthesis and bioassay of improved mosquito repellents predicted from chemical structure. Proc Natl Acad Sci USA 105(21):7359–7364. doi:10.1073/pnas.0800571105 PubMedCrossRefGoogle Scholar
  28. 28.
    Adams MD, Celniker SE, Holt RA et al (2000) The genome sequence of Drosophila melanogaster. Science 287(5461):2185–2195PubMedCrossRefGoogle Scholar
  29. 29.
    Holt RA, Subramanian GM, Halpern A et al (2002) The genome sequence of the malaria mosquito Anopheles gambiae. Science 298(5591):129–149PubMedCrossRefGoogle Scholar
  30. 30.
    Sato K, Pellegrino M, Nakagawa T, Nakagawa T, Vosshall LB, Touhara K (2008) Insect olfactory receptors are heteromeric ligand-gated ion channels. Nature 452(7190):U1002–U1006. doi:10.1038/Nature06850 CrossRefGoogle Scholar
  31. 31.
    Larsson MC, Domingos AI, Jones WD, Chiappe ME, Amrein H, Vosshall LB (2004) Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction. Neuron 43(5):703–714PubMedCrossRefGoogle Scholar
  32. 32.
    Zhou JJ (2010) Odorant-binding proteins in insects. Vitam Horm Pheromones 83:241–272. doi:10.1016/S0083-6729(10)83010-9 CrossRefGoogle Scholar
  33. 33.
    Rogers ME, Krieger J, Vogt RG (2001) Antennal SNMPs (sensor neuron membrane proteins) of lepidoptera define a unique family of invertebrate CD36-like proteins. J Neurobiol 49(1):47–61PubMedCrossRefGoogle Scholar
  34. 34.
    Benton R, Vannice KS, Vosshall LB (2007) An essential role for a CD36-related receptor in pheromone detection in Drosophila. Nature 450(7167):289–293. doi:10.1038/Nature06328 PubMedCrossRefGoogle Scholar
  35. 35.
    Merrill CE, Riesgo-Escovar J, Pitts RJ, Kafatos FC, Carlson JR, Zwiebel LJ (2002) Visual arrestins in olfactory pathways of Drosophila and the malaria vector mosquito Anopheles gambiae. Proc Natl Acad Sci USA 99(3):1633–1638. doi:10.1073/pnas.022505499 PubMedCrossRefGoogle Scholar
  36. 36.
    Vogt RG, Riddiford LM, Prestwich GD (1985) Kinetic-properties of a sex pheromone-degrading enzyme—the sensillar esterase of Antheraea polyphemus. Proc Natl Acad Sci USA 82(24):8827–8831PubMedCrossRefGoogle Scholar
  37. 37.
    Ishida Y, Leal WS (2002) Cloning of putative odorant-degrading enzyme and integumental esterase cDNAs from the wild silkmoth, Antheraea polyphemus. Insect Biochem Mol Biol 32(12):1775–1780. doi:10.1016/S0965-1748(02)00136-4
  38. 38.
    Rybczynski R, Reagan J, Lerner MR (1989) A pheromone-degrading aldehyde oxidase in the antennae of the moth Manduca sexta. J Neurosci 9(4):1341–1353PubMedGoogle Scholar
  39. 39.
    Rogers ME, Jani MK, Vogt RG (1999) An olfactory-specific glutathione-S-transferase in the sphinx moth Manduca sexta. J Exp Biol 202(Pt 12):1625–1637PubMedGoogle Scholar
  40. 40.
    Pelosi P (1996) Perireceptor events in olfaction. J Neurobiol 30(1):3–19PubMedCrossRefGoogle Scholar
  41. 41.
    Laughlin JD, Ha TS, Jones DN, Smith DP (2008) Activation of pheromone-sensitive neurons is mediated by conformational activation of pheromone-binding protein. Cell 133(7):1255–1265. doi:10.1016/j.cell.2008.04.046 Google Scholar
  42. 42.
    Du GH, Prestwich GD (1995) Protein-structure encodes the ligand-binding specificity in pheromone binding-proteins. Biochemistry 34(27):8726–8732PubMedCrossRefGoogle Scholar
  43. 43.
    MaÏbÈche-Coisne M, Sobrio F, Delaunay T, Lettere M, Dubroca J, Jacquin-Joly E, Nagnan-Le Meillour P (1997) Pheromone binding proteins of the moth Mamestra brassicae: specificity of ligand binding. Insect Biochem Mol Biol 27(3):213–221. doi:10.1016/S0965-1748(96)00088-4 CrossRefGoogle Scholar
  44. 44.
    Maida R, Krieger J, Gebauer T, Lange U, Ziegelberger G (2000) Three pheromone-binding proteins in olfactory sensilla of the two silkmoth species Antheraea polyphemus and Antheraea pernyi. Eur J Biochem 267(10):2899–2908PubMedCrossRefGoogle Scholar
  45. 45.
    Plettner E, Lazar J, Prestwich EG, Prestwich GD (2000) Discrimination of pheromone enantiomers by two pheromone binding proteins from the gypsy moth Lymantria dispar. Biochemistry 39(30):8953–8962PubMedCrossRefGoogle Scholar
  46. 46.
    Wojtasek H, Leal WS (1999) Conformational change in the pheromone-binding protein from Bombyx mori induced by pH and by interaction with membranes. J Biol Chem 274(43):30950–30956PubMedCrossRefGoogle Scholar
  47. 47.
    Leal WS, Chen AM, Erickson ML (2005) Selective and pH-dependent binding of a moth pheromone to a pheromone-binding protein. J Chem Ecol 31(10):2493–2499. doi:10.1007/s10886-005-7458-4 PubMedCrossRefGoogle Scholar
  48. 48.
    Tumlinson JH, Klein MG, Doolittle RE, Ladd TL, Proveaux AT (1977) Identification of female Japanese beetle sex-pheromone—inhibition of male response by an enantiomer. Science 197(4305):789–792PubMedCrossRefGoogle Scholar
  49. 49.
    Leal WS, Zarbin PHG, Wojtasek H, Kuwahara S, Hasegawa M, Ueda Y (1997) Medicinal alkaloid as a sex pheromone. Nature 385(6613):213PubMedCrossRefGoogle Scholar
  50. 50.
    Leal WS (1996) Chemical communication in scarab beetles: reciprocal behavioral agonist-antagonist activities of chiral pheromones. Proc Natl Acad Sci USA 93(22):12112–12115PubMedCrossRefGoogle Scholar
  51. 51.
    Leal WS (1991) (R,Z)-5-(−)-(oct-1-enyl)Oxacyclopentan-2-one, the sex-pheromone of the scarab beetle Anomala cuprea. Naturwissenschaften 78(11):521–523CrossRefGoogle Scholar
  52. 52.
    Wetzel CH, Behrendt HJ, Gisselmann G, Stortkuhl KF, Hovemann B, Hatt H (2001) Functional expression and characterization of a Drosophila odorant receptor in a heterologous cell system. Proc Natl Acad Sci USA 98(16):9377–9380PubMedCrossRefGoogle Scholar
  53. 53.
    Hallem EA, Fox AN, Zwiebel LJ, Carlson JR (2004) Olfaction—mosquito receptor for human-sweat odorant. Nature 427(6971):212–213. doi:10.1038/427212a PubMedCrossRefGoogle Scholar
  54. 54.
    Carey AF, Wang GR, Su CY, Zwiebel LJ, Carlson JR (2010) Odorant reception in the malaria mosquito Anopheles gambiae. Nature 464(7285):U66–U71. doi:10.1038/Nature08834 CrossRefGoogle Scholar
  55. 55.
    Wang GR, Carey AF, Carlson JR, Zwiebel LJ (2010) Molecular basis of odor coding in the malaria vector mosquito Anopheles gambiae. Proc Natl Acad Sci USA 107(9):4418–4423. doi:10.1073/pnas.0913392107 PubMedCrossRefGoogle Scholar
  56. 56.
    Leal WS (2005) Pheromone reception. Top Curr Chem 240:1–36. doi:10.1007/B98314 Google Scholar
  57. 57.
    Tegoni M, Campanacci V, Cambillau C (2004) Structural aspects of sexual attraction and chemical communication in insects. Trends Biochem Sci 29(5):257–264. doi:10.1016/j.tibs.2004.03.003 PubMedCrossRefGoogle Scholar
  58. 58.
    Biessmann H, Nguyen QK, Le D, Walter MF (2005) Microarray-based survey of a subset of putative olfactory genes in the mosquito Anopheles gambiae. Insect Mol Biol 14(6):575–589. doi:10.1111/j.1365-2583.2005.00590.x PubMedCrossRefGoogle Scholar
  59. 59.
    Biessmann H, Andronopoulou E, Biessmann MR, Douris V, Dimitratos SD, Eliopoulos E, Guerin PM, Iatrou K, Justice RW, Krober T, Marinotti O, Tsitoura P, Woods DF, Walter MF (2010) The Anopheles gambiae odorant binding protein 1 (AgamOBP1) mediates indole recognition in the antennae of female mosquitoes. PLoS ONE 5(3):e9471. doi:10.1371/Journal.Pone.0009471 PubMedCrossRefGoogle Scholar
  60. 60.
    Mao Y, Xu XZ, Xu W, Ishida Y, Leal WS, Ames JB, Clardy J (2010) Crystal and solution structures of an odorant-binding protein from the southern house mosquito complexed with an oviposition pheromone. Proc Natl Acad Sci USA 107(44):19102–19107. doi:10.1073/pnas.1012274107 PubMedCrossRefGoogle Scholar
  61. 61.
    Biessmann H, Walter MF, Dimitratos S, Woods D (2002) Isolation of cDNA clones encoding putative odourant binding proteins from the antennae of the malaria-transmitting mosquito, Anopheles gambiae. Insect Mol Biol 11(2):123–132PubMedCrossRefGoogle Scholar
  62. 62.
    Wogulis M, Morgan T, Ishida Y, Leal WS, Wilson DK (2006) The crystal structure of an odorant binding protein from Anopheles gambiae: evidence for a common ligand release mechanism. Biochem Biophys Res Commun 339(1):157–164. doi:10.1016/j.bbrc.2005.10.191 PubMedCrossRefGoogle Scholar
  63. 63.
    Kubala M, Plasek J, Amler E (2004) Fluorescence competition assay for the assessment of ATP binding to an isolated domain of Na+, K+-ATPase. Physiol Res 53(1):109–113PubMedGoogle Scholar
  64. 64.
    Leatherbarrow RJ (2007) GrafFit version 6.0. Erithakus Software, StainesGoogle Scholar
  65. 65.
    Leslie AGW (1992) Recent changes to the MOSFLM package for processing film and image plate data. Jnt CCP4/ESF-EACBM Newsl Protein Crystallogr No. 26Google Scholar
  66. 66.
    Collaborative Computational Project N (1994) The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50(Pt 5):760–763Google Scholar
  67. 67.
    French S, Wilson K (1978) Treatment of Negative Intensity Observations. Acta Crystallogr Sect A 34:517–525Google Scholar
  68. 68.
    Vagin A, Teplyakov A (1997) MOLREP: an automated program for molecular replacement. J Appl Crystallogr 30:1022–1025CrossRefGoogle Scholar
  69. 69.
    Emsley P, Cowtan K (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr Sect D Biol Crystallogr 60:2126–2132CrossRefGoogle Scholar
  70. 70.
    Murshudov GN, Vagin AA, Dodson EJ (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr Sect D Biol Crystallogr 53:240–255CrossRefGoogle Scholar
  71. 71.
    Schuttelkopf AW, van Aalten DM (2004) PRODRG: a tool for high-throughput crystallography of protein–ligand complexes. Acta Crystallogr D Biol Crystallogr 60(Pt 8):1355–1363. doi:10.1107/S0907444904011679 PubMedCrossRefGoogle Scholar
  72. 72.
    Painter J, Merritt EA (2006) TLSMD web server for the generation of multi-group TLS models. J Appl Crystallogr 39:109–111CrossRefGoogle Scholar
  73. 73.
    Laskowski RA, Macarthur MW, Moss DS, Thornton JM (1993) Procheck—a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283–291CrossRefGoogle Scholar
  74. 74.
    Mcdonald IK, Thornton JM (1994) Satisfying hydrogen-bonding potential in proteins. J Mol Biol 238(5):777–793PubMedCrossRefGoogle Scholar
  75. 75.
    Hubbard SJ, Thornton JM (1993) NACCESS Computer Program. Department of Biochemistry and Molecular Biology, University College LondonGoogle Scholar
  76. 76.
    Wallace AC, Laskowski RA, Thornton JM (1995) Ligplot—a program to generate schematic diagrams of protein ligand interactions. Protein Eng 8(2):127–134PubMedCrossRefGoogle Scholar
  77. 77.
    Medek P, Benes P, Sochor J (2007) Computation of tunnels in protein molecules using Delaunay triangulation. J Wscg 15(1–3):107–114 158Google Scholar
  78. 78.
    Kleywegt GJ, Jones TA (1994) Detection, delineation, measurement and display of cavities in macromolecular structures. Acta Crystallogr Sect D-Biol Crystallogr 50:178–185CrossRefGoogle Scholar
  79. 79.
    Lawrence MC, Colman PM (1993) Shape complementarity at protein–protein interfaces. J Mol Biol 234(4):946–950PubMedCrossRefGoogle Scholar
  80. 80.
    DeLano WL (2002) The PyMOL molecular graphics system. DeLano, Palo AltoGoogle Scholar
  81. 81.
    Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19(14):1639–1662CrossRefGoogle Scholar
  82. 82.
    Kuntz ID, Chen K, Sharp KA, Kollman PA (1999) The maximal affinity of ligands. Proc Natl Acad Sci USA 96(18):9997–10002PubMedCrossRefGoogle Scholar
  83. 83.
    Bembenek SD, Tounge BA, Reynolds CH (2009) Ligand efficiency and fragment-based drug discovery. Drug Discov Today 14(5–6):278–283. doi:10.1016/j.drudis.2008.11.007 PubMedCrossRefGoogle Scholar
  84. 84.
    Zhou JJ, Zhang GA, Huang W, Birkett MA, Field LM, Pickett JA, Pelosi P (2004) Revisiting the odorant-binding protein LUSH of Drosophila melanogaster: evidence for odour recognition and discrimination. FEBS Lett 558(1–3):23–26. doi:10.1016/S0014-5793(03)01521-7 PubMedCrossRefGoogle Scholar
  85. 85.
    Marie AD, Veggerby C, Robertson DHL, Gaskell SJ, Hubbard SJ, Martinsen L, Hurst JL, Beynon RJ (2001) Effect of polymorphisms on ligand binding by mouse major urinary proteins. Protein Sci 10(2):411–417CrossRefGoogle Scholar
  86. 86.
    Ban LP, Zhang L, Yan YH, Pelosi P (2002) Binding properties of a locust’s chemosensory protein. Biochem Biophys Res Commun 293(1):50–54. doi:PiiS0006-291x(02)00185-7 PubMedCrossRefGoogle Scholar
  87. 87.
    Leal WS, Barbosa RMR, Xu W, Ishida Y, Syed Z, Latte N, Chen AM, Morgan TI, Cornel AJ, Furtado A (2008) Reverse and conventional chemical ecology approaches for the development of oviposition attractants for culex mosquitoes. PLoS ONE 3(8):e3045. doi:10.1371/Journal.Pone.0003045 PubMedCrossRefGoogle Scholar
  88. 88.
    Pelosi P, Zhou JJ, Ban LP, Calvello M (2006) Soluble proteins in insect chemical communication. Cell Mol Life Sci 63(14):1658–1676. doi:10.1007/s00018-005-5607-0 PubMedCrossRefGoogle Scholar
  89. 89.
    Anderson AC (2003) The process of structure-based drug design. Chem Biol 10(9):787–797. doi:10.1016/j.chembiol.2003.09.002 PubMedCrossRefGoogle Scholar
  90. 90.
    Powers RA, Morandi F, Shoichet BK (2002) Structure-based discovery of a novel, noncovalent inhibitor of AmpC beta-lactamase. Structure 10(7):1013–1023. doi:10.1016/S0969-2126(02)00799-2 PubMedCrossRefGoogle Scholar
  91. 91.
    Lam PY, Jadhav PK, Eyermann CJ, Hodge CN, Ru Y, Bacheler LT, Meek JL, Otto MJ, Rayner MM, Wong YN et al (1994) Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors. Science 263(5145):380–384PubMedCrossRefGoogle Scholar
  92. 92.
    Pastor M, Cruciani G, Watson KA (1997) A strategy for the incorporation of water molecules present in a ligand binding site into a three-dimensional quantitative structure–activity relationship analysis. J Med Chem 40(25):4089–4102. doi:10.1021/jm970273d PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  • K. E. Tsitsanou
    • 1
  • T. Thireou
    • 2
  • C. E. Drakou
    • 1
  • K. Koussis
    • 3
  • M. V. Keramioti
    • 1
  • D. D. Leonidas
    • 4
  • E. Eliopoulos
    • 2
  • K. Iatrou
    • 3
  • S. E. Zographos
    • 1
  1. 1.Institute of Organic and Pharmaceutical ChemistryNational Hellenic Research FoundationAthensGreece
  2. 2.Department of Agricultural BiotechnologyAgricultural University of AthensAthensGreece
  3. 3.Insect Molecular Genetics and Biotechnology Group, Institute of BiologyNCSR “Demokritos”AthensGreece
  4. 4.Department of Biochemistry and BiotechnologyUniversity of ThessalyLarissaGreece

Personalised recommendations