Skip to main content

Advertisement

SpringerLink
Log in

The crystal structure of the AgamOBP1•Icaridin complex reveals alternative binding modes and stereo-selective repellent recognition

  • Original Article
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Anopheles gambiae Odorant Binding Protein 1 in complex with the most widely used insect repellent DEET, was the first reported crystal structure of an olfactory macromolecule with a repellent, and paved the way for OBP1-structure-based approaches for discovery of new host-seeking disruptors. In this work, we performed STD-NMR experiments to directly monitor and verify the formation of a complex between AgamOBP1 and Icaridin, an efficient DEET alternative. Furthermore, Isothermal Titration Calorimetry experiments provided evidence for two Icaridin-binding sites with different affinities (Kd = 0.034 and 0.714 mM) and thermodynamic profiles of ligand binding. To elucidate the binding mode of Icaridin, the crystal structure of AgamOBP1•Icaridin complex was determined at 1.75 Å resolution. We found that Icaridin binds to the DEET-binding site in two distinct orientations and also to a novel binding site located at the C-terminal region. Importantly, only the most active 1R,2S-isomer of Icaridin’s equimolar diastereoisomeric mixture binds to the AgamOBP1 crystal, providing structural evidence for the possible contribution of OBP1 to the stereoselectivity of Icaridin perception in mosquitoes. Structural analysis revealed two ensembles of conformations differing mainly in spatial arrangement of their sec-butyl moieties. Moreover, structural comparison with DEET indicates a common recognition mechanism for these structurally related repellents. Ligand interactions with both sites and binding modes were further confirmed by 2D 1H-15N HSQC NMR spectroscopy. The identification of a novel repellent-binding site in AgamOBP1 and the observed structural conservation and stereoselectivity of its DEET/Icaridin-binding sites open new perspectives for the OBP1-structure-based discovery of next-generation insect repellents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

AgamOBP1:

Odorant binding protein 1 from Anopheles gambiae

CquiOBP:

Odorant binding protein from Culex quinquefasciatus

AaegOBP1:

Odorant binding protein 1 from Aedes aegypti

OR:

Odorant receptor

Icaridin:

1:1 mixture of four racemic diastereoisomers of butan-2-yl 2-(2-hydroxyethyl)piperidine-1-carboxylate

DEET:

N,N-diethyl-3-methylbenzamide

AI3-37220:

1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine

6-MH:

6-methyl-5-heptene-2-one

MOP:

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

1-NPN:

N-phenyl-1-naphthylamine

vdW:

van der Waals

STD-NMR:

Saturation transfer difference nuclear magnetic resonance spectroscopy

HSQC:

Heteronuclear single quantum coherence

CSP:

Chemical shift perturbation

References

  1. World Health Organization (2014). A global brief on vector-borne diseases. WHO website [online] http://www.who.int/campaigns/world-health-day/2014/global-brief/en/. Accessed 27 July 2016

  2. Moore SJDM (2007) History of insect repellents. In: Debboun MFS, Strickman D (eds) Insect repellents: principles, methods, and uses. CRC, Boca Raton, pp 3–30

    Google Scholar 

  3. Panagiotakopulu E, Buckland PC, Day PM, Sarpaki AA, Doumas C (1995) Natural insecticides and insect repellents in antiquity—a review of the evidence. J Archaeol Sci 22(5):705–710. doi:10.1016/S0305-4403(95)80156-1

    Article  Google Scholar 

  4. Debboun M, Strickman D (2013) Insect repellents and associated personal protection for a reduction in human disease. Med Vet Entomol 27(1):1–9. doi:10.1111/j.1365-2915.2012.01020.x

    Article  CAS  PubMed  Google Scholar 

  5. Paluch G, Bartholomay L, Coats J (2010) Mosquito repellents: a review of chemical structure diversity and olfaction. Pest Manag Sci 66(9):925–935. doi:10.1002/ps.1974

    Article  CAS  PubMed  Google Scholar 

  6. Maia MF, Moore SJ (2011) Plant-based insect repellents: a review of their efficacy, development and testing. Malar J 10:1. doi:10.1186/1475-2875-10-S1-S11

    Article  Google Scholar 

  7. Mccabe ET, Barthel WF, Gertler SI, Hall SA (1954) Insect Repellents. 3. N, N-Diethylamides. J Org Chem 19(4):493–498

    Article  CAS  Google Scholar 

  8. Boeckh J, Breer H, Geier M, Hoever FP, Kruger BW, Nentwig G, Sass H (1996) Acylated 1,3-aminopropanols as repellents against bloodsucking arthropods. Pestic Sci 48(4):359–373

    Article  CAS  Google Scholar 

  9. WHO/CDS/CPE/WHOPES/2001.2 (2000) Report of the fourth WHOPES working group meeting : WHO/HQ, Geneva, 4–5 December 2000: review of : IR3535; KBR3023; (RS)-Methoprene 20% EC, Pyriproxyfen 0.5% GR; and Lambda-Cyhalothrin 2.5% CS, pp 21–28. http://www.who.int/iris/handle/10665/66683. Accessed 27 July 2016

  10. Centers for Disease Control and Prevention, USA (2005) CDC adopts new repellent guidance for upcoming mosquito season. Press Release, April 28, 2005. http://www.cdc.gov/media/pressrel/r050428.htm. Accessed 27 July 2016

  11. Barnard DR, Bernier UR, Posey KH, Xue RD (2002) Repellency of IR3535, KBR3023, para-menthane-3,8-diol, and deet to black salt marsh mosquitoes (Diptera : Culicidae) in the Everglades National Park. J Med Entomol 39(6):895–899. doi:10.1603/0022-2585-39.6.895

    Article  CAS  PubMed  Google Scholar 

  12. Yap HH, Jahangir K, Chong ASC, Adanan CR, Chong NL, Malik YA, Rohaizat B (1998) Field efficacy of a new repellent, KBR 3023, against Aedes albopictus (SKUSE) and Culex quinquefasciatus (SAY) in a tropical environment. J Vector Ecol 23(1):62–68

    CAS  PubMed  Google Scholar 

  13. Yap HH, Jahangir K, Zairi J (2000) Field efficacy of four insect repellent products against vector mosquitoes in a tropical environment. J Am Mosq Control Assoc 16(3):241–244

    CAS  PubMed  Google Scholar 

  14. 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):1193–1201

    Article  CAS  PubMed  Google Scholar 

  15. Xu P, Choo YM, De La Rosa A, Leal WS (2014) Mosquito odorant receptor for DEET and methyl jasmonate. Proc Natl Acad Sci USA 111(46):16592–16597. doi:10.1073/pnas.1417244111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Xu PX, Leal WS (2013) Probing insect odorant receptors with their cognate ligands: insights into structural features. Biochem Biophys Res Commun 435(3):477–482. doi:10.1016/j.bbrc.2013.05.015

    Article  CAS  PubMed  Google Scholar 

  17. Miszta P, Basak SC, Natarajan R, Nowak W (2013) How computational studies of mosquito repellents contribute to the control of vector borne diseases. Curr Comput Aided Drug Des 9(3):300–307

    Article  CAS  PubMed  Google Scholar 

  18. 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

    Article  PubMed  PubMed Central  Google Scholar 

  19. Pelletier J, Guidolin A, Syed Z, Cornel AJ, Leal WS (2010) Knockdown of a mosquito odorant-binding protein involved in the sensitive detection of oviposition attractants. J Chem Ecol 36(3):245–248. doi:10.1007/s10886-010-9762-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tsitsanou KE, Thireou T, Drakou CE, Koussis K, Keramioti MV, Leonidas DD, Eliopoulos E, Iatrou K, Zographos SE (2012) Anopheles gambiae odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents. Cell Mol Life Sci 69(2):283–297. doi:10.1007/s00018-011-0745-z

    Article  CAS  PubMed  Google Scholar 

  21. Logan JG, Stanczyk NM, Hassanali A, Kemei J, Santana AE, Ribeiro KA, Pickett JA, Mordue Luntz AJ (2010) Arm-in-cage testing of natural human-derived mosquito repellents. Malar J 9:239. doi:10.1186/1475-2875-9-239

    Article  PubMed  PubMed Central  Google Scholar 

  22. Murphy EJ, Booth JC, Davrazou F, Port AM, Jones DN (2013) Interactions of Anopheles gambiae odorant-binding proteins with a human-derived repellent: implications for the mode of action of n, n-diethyl-3-methylbenzamide (DEET). J Biol Chem 288(6):4475–4485. doi:10.1074/jbc.M112.436386

    Article  CAS  PubMed  Google Scholar 

  23. Yin J, Choo YM, Duan H, Leal WS (2015) Selectivity of odorant-binding proteins from the southern house mosquito tested against physiologically relevant ligands. Front Physiol 6:56. doi:10.3389/fphys.2015.00056

    Article  PubMed  PubMed Central  Google Scholar 

  24. Marley J, Lu M, Bracken C (2001) A method for efficient isotopic labeling of recombinant proteins. J Biomol NMR 20(1):71–75. doi:10.1023/A:1011254402785

    Article  CAS  PubMed  Google Scholar 

  25. Leatherbarrow RJ (2007) GrafFit Version 6.0. Erithakus Software, Staines, UK

  26. Capaldi S, Guariento M, Saccomani G, Fessas D, Perduca M, Monaco HL (2007) A single amino acid mutation in zebrafish (Danio rerio) liver bile acid-binding protein can change the stoichiometry of ligand binding. J Biol Chem 282(42):31008–31018. doi:10.1074/jbc.M705399200

    Article  CAS  PubMed  Google Scholar 

  27. Tripsianes K, Madl T, Machyna M, Fessas D, Englbrecht C, Fischer U, Neugebauer KM, Sattler M (2011) Structural basis for dimethylarginine recognition by the Tudor domains of human SMN and SPF30 proteins. Nat Struct Mol Biol 18(12):1414–1420. doi:10.1038/nsmb.2185

    Article  CAS  PubMed  Google Scholar 

  28. Wyman J, Gill SJ (1990) Binding and linkage: functional chemistry of biological macromolecules. University Science Books, Mill Valley, pp 49–59

    Google Scholar 

  29. Gill SJ (1989) Thermodynamics of ligand-binding to proteins. Pure Appl Chem 61(6):1009–1020. doi:10.1351/pac198961061009

    Article  CAS  Google Scholar 

  30. Press WH, Flannery BP, Teukolsky SA, Vetterling WT (1989) In Numerical recipes: The art of scientific computing, Press, C. U., ed., Cambridge, pp 521–538

  31. Cavanagh J, Fairbrother WJ, Palmer AG, Rance M, Skelton NJ (2007) Protein NMR spectroscopy: principles and practice, 2nd edn. Academic Press, San Diego

    Google Scholar 

  32. 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

    Article  CAS  PubMed  Google Scholar 

  33. Kabsch W (2010) Xds. Acta Crystallogr D Biol Crystallogr 66(Pt 2):125–132. doi:10.1107/S0907444909047337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. COLLABORATIVE COMPUTATIONAL PROJECT N (1994) The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50(Pt 5):760–763

    Article  Google Scholar 

  35. French S, Wilson K (1978) Treatment of Negative Intensity Observations. Acta Crystallographica Section A 34:517–525

  36. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ (2007) Phaser crystallographic software. J Appl Crystallogr 40(Pt 4):658–674. doi:10.1107/S0021889807021206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Emsley P, Cowtan K (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr Sect D-Biol Crystallogr 60:2126–2132

    Article  Google Scholar 

  38. Murshudov GN, Vagin AA, Dodson EJ (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr Sect D-Biol Crystallogr 53:240–255

    Article  CAS  Google Scholar 

  39. 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

    Article  PubMed  Google Scholar 

  40. Laskowski RA, Macarthur MW, Moss DS, Thornton JM (1993) Procheck—a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283–291

    Article  CAS  Google Scholar 

  41. Chen VB, Arendall WB 3rd, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, Murray LW, Richardson JS, Richardson DC (2010) MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr 66(Pt 1):12–21. doi:10.1107/S0907444909042073

    Article  CAS  PubMed  Google Scholar 

  42. Joosten RP, Long F, Murshudov GN, Perrakis A (2014) The PDB_REDO server for macromolecular structure model optimization. Iucrj 1:213–220. doi:10.1107/S2052252514009324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mcdonald IK, Thornton JM (1994) Satisfying hydrogen-bonding potential in proteins. J Mol Biol 238(5):777–793

    Article  CAS  PubMed  Google Scholar 

  44. Lawrence MC, Colman PM (1993) Shape complementarity at protein–protein interfaces. J Mol Biol 234(4):946–950

    Article  CAS  PubMed  Google Scholar 

  45. DeLano WL (2002) The PyMOL molecular graphics system. DeLano Scientific, Palo Alto

    Google Scholar 

  46. DiscoveryStudio Dassault Systèmes BIOVIA (2011) Discovery Studio Modeling Environment, Release 3.1, San Diego: Dassault Systèmes

  47. Mayer M, Meyer B (1999) Characterization of ligand binding by saturation transfer difference NMR spectroscopy. Angew Chemie-Int Ed 38(12):1784–1788. doi:10.1002/(SICI)1521-3773(19990614)38:12<1784:AID-ANIE1784>3.0.CO;2-Q

    Article  CAS  Google Scholar 

  48. Meyer B, Peters T (2003) NMR Spectroscopy techniques for screening and identifying ligand binding to protein receptors. Angew Chemie-Int Ed 42(8):864–890. doi:10.1002/anie.200390233

    Article  CAS  Google Scholar 

  49. Capaldi S, Saccomani G, Fessas D, Signorelli M, Perduca M, Monaco HL (2009) The X-ray structure of zebrafish (Danio rerio) ileal bile acid-binding protein reveals the presence of binding sites on the surface of the protein molecule. J Mol Biol 385(1):99–116. doi:10.1016/j.jmb.2008.10.007

    Article  CAS  PubMed  Google Scholar 

  50. Mao Y, Xu X, 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Leite NR, Krogh R, Xu W, Ishida Y, Iulek J, Leal WS, Oliva G (2009) Structure of an odorant-binding protein from the mosquito Aedes aegypti suggests a binding pocket covered by a pH-sensitive “Lid”. PLoS One 4(11):e8006. doi:10.1371/journal.pone.0008006

    Article  PubMed  PubMed Central  Google Scholar 

  52. Basak SC, Natarajan R, Nowak W, Miszta P, Klun JA (2007) Three dimensional structure-activity relationships (3D-QSAR) for insect repellency of diastereoisomeric compounds: a hierarchical molecular overlay approach. SAR QSAR Environ Res 18(3–4):237–250. doi:10.1080/10629360701303784

    Article  CAS  PubMed  Google Scholar 

  53. Ma D, Bhattacharjee AK, Gupta RK, Karle JM (1999) Predicting mosquito repellent potency of N,N-diethyl-m-toluamide (DEET) analogs from molecular electronic properties. Am J Trop Med Hyg 60(1):1–6

    CAS  PubMed  Google Scholar 

  54. Bhattacharjee AK, Dheranetra W, Nichols DA, Gupta RK (2005) 3D pharmacophore model for insect repellent activity and discovery of new repellent candidates. QSAR Comb Sci 24(5):593–602. doi:10.1002/qsar.200430914

    Article  CAS  Google Scholar 

  55. Bhattacharjee AK, Gupta RK (2005) Analysis of molecular stereoelectronic similarity between N,N-diethyl-m-toluamide (Deet) analogs and insect juvenile hormone to develop a model pharmacophore for insect repellent activity. J Am Mosq Control Assoc 21(4):23–29. doi:10.2987/8756-971x(2005)21[23:Aomssb]2.0.Co;2

  56. Bhattacharjee AK, Gupta RK, Ma D, Karle JM (2000) Molecular similarity analysis between insect juvenile hormone and N,N-diethyl-m-toluamide (DEET) analogs may aid design of novel insect repellents. J Mol Recognit 13(4):213–220

    Article  CAS  PubMed  Google Scholar 

  57. Klun JA, Schmidt WF, Debboun M (2001) Stereochemical effects in an insect repellent. J Med Entomol 38(6):809–812

    Article  CAS  PubMed  Google Scholar 

  58. Davrazou F, Dong E, Murphy EJ, Johnson HT, Jones DNM (2011) New insights into the mechanism of odorant detection by the malaria-transmitting mosquito Anopheles gambiae. J Biol Chem 286(39):34175–34183. doi:10.1074/jbc.M111.274712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Affonso RD, Guimaraes AP, Oliveira AA, Slana GBC, Franca TCC (2013) Applications of molecular modeling in the design of new insect repellents targeting the odorant binding protein of Anopheles gambiae. J Braz Chem Soc 24(3):473–482. doi:10.5935/0103-5053.20130059

    Article  CAS  Google Scholar 

  60. Oliferenko PV, Oliferenko AA, Poda GI, Osolodkin DI, Pillai GG, Bernier UR, Tsikolia M, Agramonte NM, Clark GG, Linthicum KJ, Katritzky AR (2013) Promising Aedes aegypti repellent chemotypes identified through integrated QSAR, virtual screening, synthesis, and bioassay. PLoS One 8(9):e64547. doi:10.1371/journal.pone.0064547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Payne TL, Dickens JC, Richerson JV (1984) Insect predator-prey coevolution via enantiomeric specificity in a kairomone-pheromone system. J Chem Ecol 10(3):487–492. doi:10.1007/BF00988094

    Article  CAS  PubMed  Google Scholar 

  62. Wadhams LJ, Angst ME, Blight MM (1982) Responses of the olfactory receptors of Scolytus scolytus (F.) (Coleoptera: Scolytidae) to the stereoisomers of 4-methyl-3-heptanol. J Chem Ecol 8(2):477–492. doi:10.1007/BF00987796

    Article  CAS  PubMed  Google Scholar 

  63. Flath RA, Cunningham RT, Mon TR, John JO (1994) Male lures for mediterranean fruitfly (Ceratitis capitata wied.): structural analogs of alpha-copaene. J Chem Ecol 20(10):2595–2609. doi:10.1007/BF02036194

    Article  CAS  PubMed  Google Scholar 

  64. Cook JI, Majeed S, Ignell R, Pickett JA, Birkett MA, Logan JG (2011) Enantiomeric selectivity in behavioural and electrophysiological responses of Aedes aegypti and Culex quinquefasciatus mosquitoes. Bull Entomol Res 101(5):541–550. doi:10.1017/S0007485311000162

    Article  CAS  PubMed  Google Scholar 

  65. Borg-Karlson AK, Tengo J, Valterova I, Unelius CR, Taghizadeh T, Tolasch T, Francke W (2003) (S)-(+)-linalool, a mate attractant pheromone component in the bee Colletes cunicularius. J Chem Ecol 29(1):1–14

    Article  CAS  PubMed  Google Scholar 

  66. Hobson KR, Wood DL, Cool LG, White PR, Ohtsuka T, Kubo I, Zavarin E (1993) Chiral specificity in responses by the bark beetle Dendroctonus valens to host kairomones. J Chem Ecol 19(9):1837–1846. doi:10.1007/BF00983790

    Article  CAS  PubMed  Google Scholar 

  67. Leal WS (1996) Chemical communication in scarab beetles: reciprocal behavioral agonist-antagonist activities of chiral pheromones. Proc Natl Acad Sci USA 93(22):12112–12115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lu T, Qiu YT, Wang G, Kwon JY, Rutzler M, Kwon HW, Pitts RJ, van Loon JJ, Takken W, Carlson JR, Zwiebel LJ (2007) Odor coding in the maxillary palp of the malaria vector mosquito Anopheles gambiae. Curr Biol 17(18):1533–1544. doi:10.1016/j.cub.2007.07.062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bohbot JD, Dickens JC (2009) Characterization of an enantioselective odorant receptor in the yellow fever mosquito Aedes aegypti. PLoS One 4(9):e7032. doi:10.1371/journal.pone.0007032

    Article  PubMed  PubMed Central  Google Scholar 

  70. 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):8953–8962

    Article  CAS  PubMed  Google Scholar 

  71. 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

    Article  PubMed  PubMed Central  Google Scholar 

  72. Lartigue A, Gruez A, Spinelli S, Riviere S, Brossut R, Tegoni M, Cambillau C (2003) The crystal structure of a cockroach pheromone-binding protein suggests a new ligand binding and release mechanism. J Biol Chem 278(32):30213–30218. doi:10.1074/jbc.M304688200

    Article  CAS  PubMed  Google Scholar 

  73. Nienaber VL, Richardson PL, Klighofer V, Bouska JJ, Giranda VL, Greer J (2000) Discovering novel ligands for macromolecules using X-ray crystallographic screening. Nat Biotechnol 18(10):1105–1108. doi:10.1038/80319

    Article  CAS  PubMed  Google Scholar 

  74. Kantsadi AL, Apostolou A, Theofanous S, Stravodimos GA, Kyriakis E, Gorgogietas VA, Chatzileontiadou DSM, Pegiou K, Skamnaki VT, Stagos D, Kouretas D, Psarra AMG, Haroutounian SA, Leonidas DD (2014) Biochemical and biological assessment of the inhibitory potency of extracts from vinification byproducts of Vitis vinifera extracts against glycogen phosphorylase. Food Chem Toxicol 67:35–43. doi:10.1016/j.fct.2014.01.055

    Article  CAS  PubMed  Google Scholar 

  75. Frederickson M, Gill AL, Padova A, Congreve MS (2003) Preparation of indoles as p38 MAP kinase inhibitors. Astex Technology Limited, UK. UK Patent WO 03/087087

  76. Congreve MS, Davis DJ, Devine L, Granata C, O’Reilly M, Wyatt PG, Jhoti H (2003) Detection of ligands from a dynamic combinatorial library by X-ray crystallography. Angew Chemie-Int Ed 42(37):4479–4482. doi:10.1002/anie.200351951

    Article  CAS  Google Scholar 

  77. Grosse-Wilde E, Svatos A, Krieger J (2006) A pheromone-binding protein mediates the bombykol-induced activation of a pheromone receptor in vitro. Chem Senses 31(6):547–555. doi:10.1093/chemse/bjj059

    Article  CAS  PubMed  Google Scholar 

  78. Pophof B (2004) Pheromone-binding proteins contribute to the activation of olfactory receptor neurons in the silkmoths Antheraea polyphemus and Bombyx mori. Chem Senses 29(2):117–125. doi:10.1093/chemse/bjh012

    Article  PubMed  Google Scholar 

  79. Pophof B (2002) Moth pheromone binding proteins contribute to the excitation of olfactory receptor cells. Naturwissenschaften 89(11):515–518. doi:10.1007/s00114-002-0364-5

    Article  CAS  PubMed  Google Scholar 

  80. Leal WS (2005) Pheromone Reception. In: Schulz S (ed) The Chemistry of Pheromones and Other Semiochemicals II: Springer Berlin Heidelberg, Berlin, Heidelberg, pp 1–36. doi:10.1007/b98314

  81. Forstner M, Breer H, Krieger J (2009) A receptor and binding protein interplay in the detection of a distinct pheromone component in the silkmoth Antheraea polyphemus. Int J Biol Sci 5(7):745–757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Grosse-Wilde E, Gohl T, Bouche E, Breer H, Krieger J (2007) Candidate pheromone receptors provide the basis for the response of distinct antennal neurons to pheromonal compounds. Eur J Neurosci 25(8):2364–2373. doi:10.1111/j.1460-9568.2007.05512.x

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful for the help and advice of Prof. Simona Golic Grdadolnik and Dr. Urška Zelenko (National Institute of Chemistry, Ljubljana, Slovenia) on the development of the expression protocol and their assistance in setting up the 3D NMR experiments for the sequence-specific assignment of 13C/15N-labeled AgamOBP1. We also thank Saltigo GmbH (Germany) for kindly providing Icaridin. We acknowledge the late Dr. Harald Biessmann and Dr. Marika F. Walter (Developmental Biology Center, University of California) for kindly providing the AgamOBP1 gene (GenBank™ Accession Number AF437884). We also would like to acknowledge Dr. Kostas Iatrou (Institute of Biosciences and Applications NCSR “Demokritos”, Greece), Dr. Elias Eliopoulos (Department of Biotechnology, Agricultural University of Athens, Greece) and Dr. Panagiotis Zoumpoulakis (Institute of Biology, Medicinal Chemistry and Biotechnology, NHRF, Greece) for helpful discussions. This work was supported by funding provided under the NSRF-Bilateral Greece-Turkey R&D cooperation 2013–2015 project “PREVENT” (GSRT 14TUR), co-Financed by the European Union and the Greek State, Ministry of Education and Religious Affairs/General Secretariat for Research and Technology (O. P. Competitiveness & Entrepreneurship (EPAN ΙΙ), ROP Macedonia–Thrace, ROP Crete and Aegean Islands, ROP Thessaly–Mainland Greece–Epirus, ROP Attica). It was also supported by the European Commission under the FP7- HEALTH-2007-2.3.2.9 project ‘‘ENAROMaTIC’’ (GA-222927) and the FP7-REGPOT-2009-1 Project ‘‘ARCADE’’ (GA-245866). Work at the Synchrotron Radiation Sources, MAX-lab, Lund, Sweden and ALBA, Barcelona, Spain, was supported by funding provided by the European Community’s Seventh Framework Programme (FP7/2007–2013) under BioStruct-X (Grant Agreement No. 283570).

Author information

Authors and Affiliations

  1. Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635, Athens, Greece

    Christina E. Drakou, Katerina E. Tsitsanou, Constantinos Potamitis, Maria Zervou & Spyros E. Zographos

  2. Department of Food, Environmental and Nutritional Sciences (DeFENS), Università degli Studi di Milano, Via Celoria 2, 20133, Milan, Italy

    Dimitrios Fessas

Authors
  1. Christina E. Drakou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katerina E. Tsitsanou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Constantinos Potamitis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dimitrios Fessas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Zervou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Spyros E. Zographos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Spyros E. Zographos.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest with the contents of this article.

Additional information

The coordinates and structure factors of the AgamOBP1•Icaridin complex have been deposited with the RCSB Protein Data Bank (http://www.rcsb.org/pdb) under accession code 5EL2.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1597 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Drakou, C.E., Tsitsanou, K.E., Potamitis, C. et al. The crystal structure of the AgamOBP1•Icaridin complex reveals alternative binding modes and stereo-selective repellent recognition. Cell. Mol. Life Sci. 74, 319–338 (2017). https://doi.org/10.1007/s00018-016-2335-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-016-2335-6

Keywords

Search

Navigation