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Structural biology of lipoxygenases: current knowledge and further development

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Abstract

Lipoxygenases (LOX) form a heterogeneous family of lipid peroxidizing enzymes, which have been implicated in the synthesis of inflammatory mediators. The involvement of LOX isoenzymes in regulation of physiological homeostasis and pathogenesis of various diseases with major health and political relevance made them potential targets for pharmacological intervention. Although the first plant lipoxygenase (soybean LOX1) was discovered more than 60 years ago, the structural aspects of these enzymes were not studied until the mid 1990s. For the time being the crystal structures of various lipoxygenase-isoforms have been reported, and X-ray coordinates for numerous enzyme-ligand complexes are also available. This review focuses on recent developments in molecular enzymology of LOX and summarizes our current knowledge on the structural basis of LOX catalysis. Hypotheses explaining the reaction specificity of different isoforms as well as evolutionary aspects are reviewed and discussed. As the review is mainly intended to cover thematic priorities, which have not been reviewed in the past, a detailed discussion of the biological function of LOX goes beyond the scope of this review.

About the Authors

I. V. Ivanov
Institute of Biochemistry, Medicine University Berlin-Charité, D-10117 Berlin, Germany; M.V. Lomonosov Moscow State University of Fine Chemical Technologies, 86, Vernadskogo pr., Moscow 119571
Russian Federation


N. V. Groza
M.V. Lomonosov Moscow State University of Fine Chemical Technologies, 86, Vernadskogo pr., Moscow 119571
Russian Federation


G. I. Myagkova
M.V. Lomonosov Moscow State University of Fine Chemical Technologies, 86, Vernadskogo pr., Moscow 119571
Russian Federation


H. Kühn
Institute of Pharmacology and Toxycology, Medicine University of Rostock, D-18057 Rostock
Germany


References

1. Brash A.R. Lipoxygenases: Occurrence, functions, catalysis, and acquisition of substrate // J. Biol. Chem. 1999. V. 274. P. 23679-23682.

2. Kuhn H., Saam J., Eibach S., Holzhutter H.G., Ivanov I., Walther M. Structural biology of mammalian lipoxygenases: Enzymatic consequences of targeted alterations of the protein structure // Biochem. Biophys. Res. Commun. 2005. V. 338. P. 93-101.

3. Schneider C., Pratt D.A., Porter N.A., Brash A.R. Control of oxygenation in lipoxygenase and cyclooxygenase catalysis // Chem. Biol. 2007. V. 14. P. 473-488.

4. Glickman M.H., Klinman J.P. Nature of rate-limiting steps in the soybean lipoxygenase-1 reaction // Biochemistry. 1995. V. 34. P. 14077-14092.

5. Rickert K.W., Klinman J.P. Nature of hydrogen transfer in soybean lipoxygenase 1: Separation of primary and secondary isotope effects // Biochemistry. 1999. V. 38. P. 12218-12228.

6. Lehnert N., Solomon E.I. Density-functional investigation on the mechanism of H-atom abstraction by lipoxygenase // J. Biol. Inorg. Chem. 2003. V. 8. P. 294-305.

7. Hatcher E., Soudackov A.V., Hammes-Schiffer S. Proton-coupled electron transfer in soybean lipoxygenase // J. Am. Chem. Soc. 2004. V. 126. P. 5763-5775.

8. Upston J.M., Neuzil J., Witting P.K., Alleva R., Stocker R. Oxidation of free fatty acids in low density lipoprotein by 15-lipoxygenase stimulates nonenzymic, alpha-tocopherol-mediated peroxidation of cholesteryl esters // J. Biol. Chem. 1997. V. 272. P. 30067-30074.

9. Takahashi Y., Glasgow W.C., Suzuki H., Taketani Y., Yamamoto S., Anton M., Kuhn H., Brash A.R. Investigation of the oxygenation of phospholipids by the porcine leukocyte and human platelet arachidonate 12-lipoxygenases // Eur. J. Biochem. 1993. V. 218. P. 165-171.

10. Schewe T., Halangk W., Hiebsch C., Rapoport S.M. A lipoxygenase in rabbit reticulocytes which attacks phospholipids and intact mitochondria // FEBS Lett. 1975. V. 60. P. 149-152.

11. Andreou A., Feussner I. Lipoxygenases - Structure and reaction mechanism // Phytochemistry. 2009. V. 70. P. 1504-1510.

12. Bhattacharya S., Mathew G., Jayne D.G., Pelengaris S., Khan M. 15-Lipoxygenase-1 in colorectal cancer: a review // Tumour Biol. 2009. V. 30. P. 185-199.

13. Pidgeon G.P., Lysaght J., Krishnamoorthy S., Reynolds J.V., O’Byrne K., Nie D., Honn K.V. Lipoxygenase metabolism: Roles in tumor progression and survival // Cancer Metastasis Rev. 2007. V. 26. P. 503-524.

14. Chawengsub Y., Gauthier K.M., Campbell W.B. Role of arachidonic acid lipoxygenase metabolites in the regulation of vascular tone // Am. J. Physiol. Heart Circ. Physiol. 2009. V. 297. P. 495-507.

15. Mochizuki N., Kwon Y.G. 15-Lipoxygenase-1 in the vasculature: Expanding roles in angiogenesis // Circ. Res. 2008. V. 102. P. 143-145.

16. Duroudier N.P., Tulah A.S., Sayers I. Leukotriene pathway genetics and pharmacogenetics in allergy // Allergy. 2009. V. 64. P. 823-839.

17. Hersberger M. Potential role of the lipoxygenase derived lipid mediators in atherosclerosis: Leukotrienes, lipoxins and resolvins. // Clin. Chem. Lab. Med. 2010. V. 12. P. 1063-1073.

18. Meyer M.P., Tomchick D.R., Klinman J.P. Enzyme structure and dynamics affect hydrogen tunneling: The impact of a remote side chain (I553) in soybean lipoxygenase-1 // Proc. Natl. Acad. Sci. USA. 2008. V. 105. P. 1146-1151.

19. Tomchick D.R., Phan P., Cymborowski M., Minor W., Holman T.R. Structural and functional characterization of second-coordination sphere mutants of soybean lipoxygenase-1 // Biochemistry. 2001. V. 40. P. 7509-7517.

20. Minor W., Solomon E.I., Holman T.R. Kinetic, spectroscopic, and structural investigations of the soybean lipoxygenase-1 first-coordination sphere mutant, Asn694Gly // Biochemistry. 2006. V. 45. P. 10233-10242.

21. Boyington J.C., Gaffney B.J., Amzel L.M. Structure of soybean lipoxygenase-I // Biochem. Soc. Trans. 1993. V. 21. P. 744-748.

22. Minor W., Steczko J., Stec B., Otwinowski Z., Bolin J.T., Walter R., Axelrod B. Crystal structure of soybean lipoxygenase L-1 at 1.4 Å resolution // Biochemistry. 1996. V. 35. P. 10687-10701.

23. Skrzypczak-Jankun E., Amzel L.M., Kroa B.A., Funk Jr. M.O. Structure of soybean lipoxygenase L3 and a comparison with its L1 isoenzyme // Proteins. 1997. V. 29. P. 15-31.

24. Skrzypczak-Jankun E., Borbulevych O.Y., Zavodszky M.I., Baranski M.R., Padmanabhan K., Petricek V., Jankun J. Effect of crystal freezing and small-molecule binding on internal cavity size in a large protein: X-ray and docking studies of lipoxygenase at ambient and low temperature at 2.0 Å resolution // Acta Crystallogr. Sect. D. Biol. Crystallogr. 2006. V. 62. P. 766-775.

25. Youn B., Sellhorn G.E., Mirchel R.J., Gaffney B.J., Grimes H.D., Kang C. Crystal structures of vegetative soybean lipoxygenase VLX-B and VLX-D, and comparisons with seed isoforms LOX-1 and LOX-3 // Proteins. 2006. V. 65. P. 1008-1020.

26. Skrzypczak-Jankun E., Zhou K., McCabe N.P., Selman S.H., Jankun J. Structure of curcumin in complex with lipoxygenase and its significance in cancer // Int. J. Mol. Med. 2003. V. 12. P. 17-24.

27. Skrzypczak-Jankun E., Bross R.A., Carroll R.T., Dunham W.R., Funk Jr. M.O. Three dimensional structure of a purple lipoxygenase // J. Am. Chem. Soc. 2001. V. 123. P. 10814-10820.

28. Borbulevych O.Y., Jankun J., Selman S.H., Skrzypczak-Jankun E. Lipoxygenase interactions with natural flavonoid, quercetin, reveal a complex with protocatechuic acid in its X-ray structure at 2.1 Å resolution // Proteins. 2004. V. 54. P. 13-19.

29. Skrzypczak-Jankun E., Zhou K., Jankun J. Inhibition of lipoxygenase by (-)-epigallocatechin gallate: X-ray analysis at 2.1 Å reveals degradation of EGCG and shows soybean LOX-3 complex with EGC instead // Int. J. Mol. Med. 2003. V. 12. P. 415-420.

30. Skrzypczak-Jankun E., Borbulevych O.Y., Jankun J. Soybean lipoxygenase-3 in complex with 4-nitrocatechol // Acta Crystallogr. Sect. D Biol. Crystallogr. 2004. V. 60. P. 613-615.

31. Pham C., Jankun J., Skrzypczak-Jankun E., Flowers 2nd R.A., Funk Jr. M.O. Structural and thermo-chemical characterization of lipoxygenase catechol complexes // Biochemistry. 1998. V. 37. P. 17952-17957.

32. Gillmor S.A., Villasenor A., Fletterick R., Sigal E., Browner M.F. The structure of mammalian 15-lipoxygenase reveals similarity to the lipases and the determinants of substrate specificity // Nat. Struct. Biol. 1997. V. 4. P. 1003-1009.

33. Choi J., Chon J.K., Kim S., Shin W. Conformational flexibility in mammalian 15S-lipoxygenase: Reinterpretation of the crystallographic data // Proteins. 2008. V. 70. P. 1023-1032.

34. Kobe M.J., Neau D.B, Mitchell C.E., Bartlett S.G., Newcomer M.E. The structure of human 15-lipoxygenase-2 with a substrate mimic // J. Biol. Chem. 2014. [Epub ahead of print].

35. Oldham M.L., Brash A.R., Newcomer M.E. Insights from the X-ray crystal structure of coral 8R-lipoxygenase: Calcium activation via a C2-like domain and a structural basis of product chirality // J. Biol. Chem. 2005. V. 280. P. 39545-39552.

36. Neau D.B., Gilbert N.C., Bartlett S.G., Boeglin W., Brash A.R., Newcomer M.E. The 1.85 Å structure of an 8R-lipoxygenase suggests a general model for lipoxygenase product specificity // Biochemistry. 2009. V. 48. P. 7906-7915.

37. Gilbert N.C., Niebuhr M., Tsuruta H., Bordelon T., Ridderbusch O., Dassey A., Brash A.R., Bartlett S.G., Newcomer M.E. A covalent linker allows for membrane targeting of an oxylipin biosynthetic complex // Biochemistry. 2008. V. 47. P. 10665-10676.

38. Tresaugues L., Moshe M., Arrowsmith C.H. [et al.] Crystal structure of the lipoxygenase domain of human arachidonate 12-lipoxygenase, 12s-type /PDB Deposition Date: 2008/5/12 (unpublished data).

39. Gilbert N.C., Bartlett S.G., Waight M.T., Neau D.B., Boeglin W.E., Brash A.R., Newcomer M.E. The structure of human 5-lipoxygenase // Science. 2011. V. 331. P. 217-219.

40. Eek P., Järving R., Järving I., Gilbert N.C., Newcomer M.E., Samel N. Structure of a calcium-dependent 11R-lipoxygenase suggests a mechanism for Ca2+ regulation // J. Biol. Chem. 2012. V. 287. P. 22377-22386.

41. Xu S., Mueser T.C., Marnett L.J., Funk Jr. M.O. Crystal structure of 12-lipoxygenase catalytic-domain-inhibitor complex identifies a substrate-binding channel for catalysis // Structure. 2012. V. 20. P. 1490-1497.

42. Koljak R., Boutaud O., Shieh B.H., Samel N., Brash A.R. Identification of a naturally occurring peroxidase-lipoxygenase fusion protein // Science. 1997. V. 277. P. 1994-1996.

43. Boutaud O., Brash A.R. Purification and catalytic activities of the two domains of the allene oxide synthase-lipoxygenase fusion protein of the coral Plexaura homomalla // J. Biol. Chem. 1999. V. 274. P. 33764-33770.

44. Abraham B.D., Sono M., Boutaud O., Shriner A., Dawson J.H., Brash A.R., Gaffney B.J. Characterization of the coral allene oxide synthase active site with UV-visible absorption, magnetic circular dichroism, and electron paramagnetic resonance spectroscopy: Еvidence for tyrosinate ligation to the ferric enzyme heme iron // Biochemistry. 2001. V. 40. P. 2251-2259.

45. Oldham M.L., Brash A.R., Newcomer M.E. The structure of coral allene oxide synthase reveals a catalase adapted for metabolism of a fatty acid hydroperoxide // Proc. Natl. Acad. Sci. USA. 2005. V. 102. P. 297-302.

46. Lohelaid H., Jarving R., Valmsen K., Varvas K., Kreen M., Jarving I., Samel N. Identification of a functional allene oxide synthase-lipoxygenase fusion protein in the soft coral Gersemia fruticosa suggests the generality of this pathway in octocorals // Biochim. Biophys. Acta. 2008. V. 1780. P. 315-321.

47. Zheng Y., Boeglin W.E., Schneider C., Brash A.R. A 49 KD mini-lipoxygenase from Anabaena sp. PCC 7120 retains catalytically complete functionality // J. Biol. Chem. 2008. V. 283. P. 5138-5147.

48. Schneider C., Niisuke K., Boeglin W.E., Voehler M., Stec D.F., Porter N.A., Brash A.R. Enzymatic synthesis of a bicyclobutane fatty acid by a hemoprotein-lipoxygenase fusion protein from the cyanobacterium Anabaena PCC 7120 // Proc. Natl. Acad. Sci. USA. 2007. V. 104. P. 18941-18945.

49. Gao B., Boeglin W.E., Zheng Y., Schneider C., Brash A.R. Evidence for an ionic intermediate in the transformation of fatty acid hydroperoxide by a catalase-related allene oxide synthase from the cyanobacterium Acaryochloris marina // J. Biol. Chem. 2009. V. 284. P. 22087-22098.

50. Chahinian H., Sias B., Carriere F. The C-terminal domain of pancreatic lipase: Functional and structural analogies with C2 domains // Curr. Protein Pept. Sci. 2000. V. 1. P. 91-103.

51. Maccarrone M., Salucci M.L. Tryptic digestion of soybean lipoxygenase-1 generates a 60 kDa fragment with improved activity and membrane binding ability // Biochemistry. 2001. V. 40. P. 6819-6827.

52. Dainese E., Angelucci C.B., Sabatucci A., De Filippis V., Mei G., Maccarrone M. A novel role for iron in modulating the activity and membrane-binding ability of a trimmed soybean lipoxygenase-1 // FASEB J. 2010. V. 24. P. 1725-1736.

53. Walther M., Anton M., Wiedmann M., Fletterick R., Kuhn H. The N-terminal domain of the reticulocyte-type 15-lipoxygenase is not essential for enzymatic activity but contains determinants for membrane binding // J. Biol. Chem. 2002. V. 277. P. 27360-27366.

54. Romanov S., Wiesner R., Myagkova G., Kuhn H., Ivanov I. Affinity labeling of the rabbit 12/15-lipoxygenase using azido derivatives of arachidonic acid // Biochemistry. 2006. V. 45. P. 3554-3562.

55. Winkler F.K., D’Arcy A., Hunziker W. Structure of human pancreatic lipase // Nature. 1990. V. 343. P. 771-774.

56. May C., Hohne M., Gnau P., Schwennesen K., Kindl H. The N-terminal β-barrel structure of lipid body lipoxygenase mediates its binding to liposomes and lipid bodies // Eur. J. Biochem. 2000. V. 267. P. 1100-1109.

57. Tatulian S.A., Steczko J., Minor W. Uncovering a calcium-regulated membrane-binding mechanism for soybean lipoxygenase-1 // Biochemistry. 1998. V. 37. P. 15481-15490.

58. Kulkarni S., Das S., Funk C.D., Murray D., Cho W. Molecular basis of the specific subcellular localization of the C2-like domain of 5-lipoxygenase // J. Biol. Chem. 2002. V. 277. P. 13167-13174.

59. Walther M., Wiesner R., Kuhn H. Investigations into calcium-dependent membrane association of 15-lipoxygenase-1. Mechanistic roles of surface-exposed hydrophobic amino acids and calcium // J. Biol. Chem. 2004. V. 279. P. 3717-3725.

60. Hammarberg T., Provost P., Persson B., Radmark O. The N-terminal domain of 5-lipoxygenase binds calcium and mediates calcium stimulation of enzyme activity // J. Biol. Chem. 2000. V. 275. P. 38787-38793.

61. Chen X.S., Funk C.D. The N-terminal “β-barrel” domain of 5-lipoxygenase is essential for nuclear membrane translocation // J. Biol. Chem. 2001. V. 276. P. 811-818.

62. Brinckmann R., Schnurr K., Heydeck D., Rosenbach T., Kolde G., Kuhn H. Membrane translocation of 15-lipoxygenase in hematopoietic cells is calcium-dependent and activates the oxygenase activity of the enzyme // Blood. 1998. V. 91. P. 64-74.

63. Schenk G., Neidig M.L., Zhou J., Holman T.R., Solomon E.I. Spectroscopic characterization of soybean lipoxygenase-1 mutants: The role of second coordination sphere residues in the regulation of enzyme activity // Biochemistry. 2003. V. 42. P. 7294-7302.

64. Kuban R.J., Wiesner R., Rathman J., Veldink G., Nolting H., Sole V.A., Kuhn H. The iron ligand sphere geometry of mammalian 15-lipoxygenases // Biochem. J. 1998. V. 332 (Pt 1). P. 237-242.

65. Dainese E., Sabatucci A., van Zadelhoff G., Angelucci C.B., Vachette P., Veldink G.A., Agrò A.F., Maccarrone M. Structural stability of soybean lipoxygenase-1 in solution as probed by small angle X-ray scattering // J. Mol. Biol. 2005. V. 349. P. 143-152.

66. Mei G., Di Venere A., Nicolai E., Angelucci C.B., Ivanov I., Sabatucci A., Dainese E., Kuhn H., Maccarrone M. Structural properties of plant and mammalian lipoxygenases. Temperature-dependent conformational alterations and membrane binding ability // Biochemistry. 2008. V. 47. P. 9234-9242.

67. Hammel M., Walther M., Prassl R., Kuhn H. Structural flexibility of the N-terminal beta-barrel domain of 15-lipoxygenase-1 probed by small angle X-ray scattering. Functional consequences for activity regulation and membrane binding // J. Mol. Biol. 2004. V. 343. P. 917-929.

68. Borngraber S., Browner M., Gillmor S., Gerth C., Anton M., Fletterick R., Kuhn H. Shape and specificity in mammalian 15-lipoxygenase active site. The functional interplay of sequence determinants for the reaction specificity // J. Biol. Chem. 1999. V. 274. P. 37345-37350.

69. Borngraber S., Kuban R.J., Anton M., Kuhn H. Phenylalanine 353 is a primary determinant for the positional specificity of mammalian 15-lipoxygenases // J. Mol. Biol. 1996. V. 264. P. 1145-1153.

70. Knapp M.J., Klinman J.P. Kinetic studies of oxygen reactivity in soybean lipoxygenase-1 // Biochemistry. 2003. V. 42. P. 11466-11475.

71. Chu K., Vojtchovsky J., McMahon B.H., Sweet R.M., Berendzen J., Schlichting I. Structure of a ligand-binding intermediate in wild-type carbonmonoxy myoglobin // Nature. 2000. V. 403. P. 921-923.

72. Ostermann A., Waschipky R., Parak F.G., Nienhaus G.U. Ligand binding and conformational motions in myoglobin // Nature. 2000. V. 404. P. 205-208.

73. Scott E.E., Gibson Q.H. Ligand migration in sperm whale myoglobin // Biochemistry. 1997. V. 36. P. 11909-11917.

74. Knapp M.J., Seebeck F.P., Klinman J.P. Steric control of oxygenation regiochemistry in soybean lipoxygenase-1 // J. Am. Chem. Soc. 2001. V. 123. P. 2931-2932.

75. Saam J., Ivanov I., Walther M., Holzhutter H.G., Kuhn H. Molecular dioxygen enters the active site of 12/15-lipoxygenase via dynamic oxygen access channels // Proc. Natl. Acad. Sci. USA. 2007. V. 104. P. 13319-13324.

76. Hamberg M., Samuelsson B. On the specificity of the oxygenation of unsaturated fatty acids catalyzed by soybean lipoxidase // J. Biol. Chem. 1967. V. 242. P. 5329-5335.

77. Kuhn H., Sprecher H., Brash A.R. On singular or dual positional specificity of lipoxygenases // J. Biol. Chem. 1990. V. 265. P. 16300-16305.

78. Kuhn H., Schewe T., Rapoport S.M. The stereochemistry of the reactions of lipoxygenases and their metabolites. Proposed nomenclature of lipoxygenases and related enzymes // Adv. Enzymol. Relat. Areas Mol. Biol. 1986. V. 58. P. 273-311.

79. Browner M., Gillmor S.A., Fletterick R. Burying a charge // Nat. Struct. Biol. 1998. V. 5. P. 179.

80. Prigge S.T., Gaffney B.J., Amzel L.M. Relation between positional specificity and chirality in mammalian lipoxygenases // Nat. Struct. Biol. 1998. V. 5. P. 178-179.

81. Hornung E., Walther M., Kuhn H., Feussner I. Conversion of cucumber linoleate 13-lipoxygenase to a 9-lipoxygenating species by site-directed mutagenesis // Proc. Natl. Acad. Sci. USA. 1999. V. 96. P. 4192-4197.

82. Gardner H.W. Soybean lipoxygenase-1 enzymically forms both (9S)- and (13S)-hydroperoxides from linoleic acid by a pH-dependent mechanism // Biochim. Biophys. Acta. 1989. V. 1001. P. 274-281.

83. Walther M., Roffeis J., Jansen C., Anton M., Ivanov I., Kuhn H. Structural basis for pH-dependent alterations of reaction specificity of vertebrate lipoxygenase isoforms // Biochim. Biophys. Acta. 2009. V. 1791. P. 827-835.

84. Walther M., Ivanov I., Myagkova G., Kuhn H. Alterations of lipoxygenase specificity by targeted substrate modification and site-directed mutagenesis // Chem. Biol. 2001. V. 8. P. 779-790.

85. Meruvu S., Walther M., Ivanov I., Hammarstrom S., Furstenberger G., Krieg P., Reddanna P., Kuhn H. Sequence determinants for the reaction specificity of murine (12R)-lipoxygenase: Targeted substrate modification and site-directed mutagenesis // J. Biol. Chem. 2005. V. 280. P. 36633-36641.

86. Coffa G., Brash A.R. A single active site residue directs oxygenation stereospecificity in lipoxy-genases: Stereocontrol is linked to the position of oxygenation // Proc. Natl. Acad. Sci. USA. 2004. V. 101. P. 15579-15584.

87. Coffa G., Schneider C., Brash A.R. A comprehensive model of positional and stereo control in lipoxy-genases // Biochem. Biophys. Res. Commun. 2005. V. 338. P. 87-92.

88. Coffa G., Imber A.N., Maguire B.C., Laxmikanthan G., Schneider C., Gaffney B.J., Brash A.R. On the relationships of substrate orientation, hydrogen abstraction, and product stereochemistry in single and double dioxygenations by soybean lipoxygenase-1 and its Ala542Gly mutant // J. Biol. Chem. 2005. V. 280. P. 38756-38766.

89. Boeglin W.E., Itoh A., Zheng Y., Coffa G., Howe G.A., Brash A.R. Investigation of substrate binding and product stereochemistry issues in two linoleate 9-lipoxygenases // Lipids. 2008. V. 43. P. 979-987.

90. Sloane D.L., Leung R., Barnett J., Craik C.S., Sigal E. Conversion of human 15-lipoxygenase to an efficient 12-lipoxygenase: The side-chain geometry of amino acids 417 and 418 determine positional specificity // Protein Eng. 1995. V. 8. P. 275-282.

91. Sloane D.L., Leung R., Craik C.S., Sigal E. A primary determinant for lipoxygenase positional specificity // Nature. 1991. V. 354. P. 149-152.

92. Vogel R., Jansen C., Roffeis J., Reddanna P., Forsell P., Claesson H.E., Kuhn H., Walther M. Applicability of the triad concept for the positional specificity of mammalian lipoxygenases // J. Biol. Chem. 2010. V. 285. P. 5369-5376.

93. Burger F., Krieg P., Marks F., Furstenberger G. Enzymic characterization of epidermis-derived 12-lipoxygenase isoenzymes // Biochem. J. 2000. V. 348 (Pt 2). P. 329-335.

94. Watanabe T., Haeggstrom J.Z. Rat 12-lipoxygenase: Mutations of amino acids implicated in the positional specificity of 15- and 12-lipoxygenases // Biochem. Biophys. Res. Commun. 1993. V. 192. P. 1023-1029.

95. Suzuki H., Kishimoto K., Yoshimoto T., Yamamoto S., Kanai F., Ebina Y., Miyatake A., Tanabe T. Site-directed mutagenesis studies on the iron-binding domain and the determinant for the substrate oxygenation site of porcine leukocyte arachidonate 12-lipoxygenase // Biochim. Biophys. Acta. 1994. V. 1210. P. 308-316.

96. Schwarz K., Walther M., Anton M., Gerth C., Feussner I., Kuhn H. Structural basis for lipoxygenase specificity. Conversion of the human leukocyte 5-lipoxygenase to a 15-lipoxygenating enzyme species by site-directed mutagenesis // J. Biol. Chem. 2001. V. 276. P. 773-779.

97. Hornung E., Rosahl S., Kuhn H., Feussner I. Creating lipoxygenases with new positional specificities by site-directed mutagenesis // Biochem. Soc. Trans. 2000. V. 28. P. 825-826.

98. Toledo L., Masgrau L., Marechal J.D., Lluch J.M., Gonzalez-Lafont A. nsights into the mechanism of binding of arachidonic acid to mammalian 15-lipoxygenases // J. Phys. Chem. B. 2010. V. 114. P. 7037-7046.

99. Toledo L., Masgrau L., Lluch J.M., Gonzalez-Lafont A. Substrate binding to mammalian 15-lipoxygenase // J. Comput. Aided Mol. Des. 2011. V. 25. P. 825-835.

100. Jisaka M., Kim R.B., Boeglin W.E., Brash A.R. Identification of amino acid determinants of the positional specificity of mouse 8S-lipoxygenase and human 15S-lipoxygenase-2 // J. Biol. Chem. 2000. V. 275. P. 1287-1293.

101. Veldink G.A., Garssen G.J., Vliegenthart J.F., Boldingh J. Positional specificity of corn germ lipoxygenase as a function of pH // Biochem. Biophys. Res. Commun. 1972. V. 47. P. 22-26.

102. Hornung E., Kunze S., Liavonchanka A., Zimmermann G., Kuhn D., Fritsche K., Renz A., Kuhn H., Feussner I. Identification of an amino acid determinant of pH regiospecificity in a seed lipoxygenase from Momordica charantia // Phytochemistry. 2008. V. 69. P. 2774-2780.

103. Falgueyret J.P., Denis D., Macdonald D., Hutchinson J.H., Riendeau D. Characterization of the arachidonate and ATP binding sites of human 5-lipoxygenase using photoaffinity labeling and enzyme immobilization // Biochemistry. 1995. V. 34. P. 13603-13611.

104. Mogul R., Johansen E., Holman T.R. Oleyl sulfate reveals allosteric inhibition of soybean lipoxygenase-1 and human 15-lipoxygenase // Biochemistry. 2000. V. 39. P. 4801-4807.

105. Wecksler A.T., Jacquot C., van der Donk W.A., Holman T. Mechanistic investigations of human reticulocyte 15- and platelet 12-lipoxygenases with arachidonic acid // Biochemistry. 2009. V. 48. P. 6259-6267.

106. Wecksler A.T., Kenyon V., Deschamps J.D., Holman T.R. Substrate specificity changes for human reticulocyte and epithelial 15-lipoxygenases reveal allosteric product regulation // Biochemistry. 2008. V. 47. P. 7364-7375.

107. Wecksler A.T., Garcia N.K., Holman T.R. Substrate specificity effects of lipoxygenase products and inhibitors on soybean lipoxygenase-1 // Bioorg. Med. Chem. 2009. V. 17. P. 6534-6539.

108. Ivanov I., Shang W., Toledo L., Masgrau L., Svergun D.I., Stehling S., Gomez H., Di Venere A., Mei G., Lluch J.M., Skrzypczak-Jankun E., Gonzalez-Lafont A., Kuhn H. Ligand-induced formation of transient dimers of mammalian 12/15-lipoxygenase: A key to allosteric behavior of this class of enzymes? // Proteins. 2012. V. 80. P. 703-712.

109. Aleem A.M., Jankun J., Dignam J.D., Walther M., Kuhn H., Svergun D.I., Skrzypczak-Jankun E. Human platelet 12-lipoxygenase, new findings about its activity, membrane binding and low-resolution structure // J. Mol. Biol. 2008. V. 376. P. 193-209.

110. Häfner A.K., Cernescu M., Hofmann B., Ermisch M., Hörnig M., Metzner J., Schneider G., Brutschy B., Steinhilber D. Dimerization of human 5-lypoxygenase // Biol. Chem. 2011. V. 392. P. 1097-1111.

111. Oliw E.H. Plant and fungal lipoxygenases // Prostaglandins Other Lipid Mediators. 2002. V. 68-69. P. 313-323.

112. De Petrocellis L., Di Marzo V. Aquatic invertebrates open up new perspectives in eicosanoid research: Biosynthesis and bioactivity // Prostaglandins Leukotrienes Essent. Fatty Acids 1994. V. 51. P. 215-229.

113. Hawkins D.J., Brash A.R. Eggs of the sea urchin, Strongylocentrotus purpuratus, contain a prominent (11R) and (12R) lipoxygenase activity // J. Biol. Chem. 1987. V. 262. P. 7629-7634.

114. Porta H., Rocha-Sosa M. Lipoxygenases in bacteria: Horizontal transfer event? // Microbiology. 2001. V. 147. P. 3199-3200.

115. Vance R.E., Hong S., Gronert K., Serhan C.N., Mekalanos J.J. The opportunistic pathogen Pseudomonas aeruginosa carries a secretable arachidonate 15-lipoxygenase // Proc. Natl. Acad. Sci. USA. 2004. V. 101. P. 2135-2139.

116. Koeduka T., Kajiwara T., Matsui K. Cloning of lipoxygenase genes from a cyanobacteria, Nostoc punctiforme, and its expression in Eschelichia coli // Curr. Microbiol. 2007. V. 54. P. 315-319.

117. Srivastava M., Begovic E., Chapman J., Putnam N.H., Hellsten U., Kawashima T., Kuo A., Mitros T., Salamov A., Carpenter M.L., Signorovitch A.Y., Moreno M.A., Kamm K., Grimwood J., Schmutz J., Shapiro H., Grigoriev I.V., Buss L.W., Schierwater B., Dellaporta S.L., Rokhsar D.S. The Trichoplax genome and the nature of placozoans // Nature. 2008. V. 454. P. 955-960.

118. Bannenberg G., Martinez M., Hamberg M., Castresana C. Diversity of the enzymatic activity in the lipoxygenase gene family of Arabidopsis thaliana // Lipids. 2009. V. 44. P. 85-95.

119. Toh H., Yokoyama C., Tanabe T., Yoshimoto T., Yamamoto S. Molecular evolution of cyclo-oxygenase and lipoxygenase // Prostaglandins. 1992. V. 44. P. 291-315.

120. Shin J.H., Van K., Kim D.H., Kim K.D., Jang Y.E., Choi B.S., Kim M.Y., Lee S.H. The lipoxygenase gene family: A genomic fossil of shared polyploidy between Glycine max and Medicago truncatula // BMC Plant Biol. 2008. V. 8. P. 133.

121. Andreou A.Z., Vanko M., Bezakova L., Feussner I. Properties of a mini 9R-lipoxygenase from Nostoc sp. PCC 7120 and its mutant forms // Phytochemistry. 2008. V. 69. P. 1832-1837.

122. Lang I., Feussner I. Oxylipin formation in Nostoc punctiforme (PCC73102) // Phytochemistry. 2007. V. 68. P. 1120-1127.

123. Lang I., Gobel C., Porzel A., Heilmann I., Feussner I. A lipoxygenase with linoleate diol synthase activity from Nostoc sp. PCC 7120 // Biochem. J. 2008. V. 410. P. 347-357.

124. Andreou A., Gobel C., Hamberg M., Feussner I. A bisallylic mini-lipoxygenase from cyanobacterium Cyanothece sp. that has an iron as cofactor // J. Biol. Chem. 2010. V. 285. P. 14178-14186.

125. Mereschkowski C. Über Natur und Ursprung der Chromatophoren im Pflanzenreiche // Biol. Centralbl. 1905. B. 25. S. 593-604.

126. Sagan L. On the origin of mitosing cells // J. Theor. Biol. 1967. V. 14. P. 255-274.

127. Huang C.Y., Ayliffe M.A., Timmis J.N. Direct measurement of the transfer rate of chloroplast DNA into the nucleus // Nature. 2003. V. 422. P. 72-76.

128. Maliga P. Plant biology: Mobile plastid genes // Nature. 2003. V. 422. P. 31-32.

129. Huang C.Y., Ayliffe M.A., Timmis J.N. Simple and complex nuclear loci created by newly transferred chloroplast DNA in tabacco // Proc. Natl. Acad. Sci. USA. 2004. V. 101. P. 9710-9715.

130. Timmis J.N., Ayliffe M.A., Huang C.Y., Martin W. Endosymbiotic gene transfer: Organelle genomes forge eukaryotic chromosomes // Nat. Rev. Genet. 2004. V. 5. P. 123-135.

131. Martin W., Stoebe B., Goremykin V., Hapsmann S., Hasegawa M., Kowallik K.V. Gene transfer to the nucleus and the evolution of chloroplasts // Nature. 1998. V. 393. P. 162-165.

132. Barsan C., Sanchez-Bel P., Rombaldi C., Egea I., Rossignol M., Kuntz M., Zouine M., Latche A., Bouzayen M., Pech J.C. Characteristics of the tomato chromoplast revealed by proteomic analysis // J. Exp. Bot. 2010. V. 61. P. 2413-2431.

133. Johannesson M., Backman L., Claesson H.E., Forsell P.K. Cloning, purification and characterization of non-human primate 12/15-lipoxygenases // Prostaglandins Leukotrienes Essent. Fatty Acids. 2010. V. 82. P. 121-129.

134. Yoshimoto T., Suzuki H., Yamamoto S., Takai T., Yokoyama C., Tanabe T. Cloning and sequence analysis of the cDNA for arachidonate 12-lipoxygenase of porcine leukocytes // Proc. Natl. Acad. Sci. USA. 1990. V. 87. P. 2142-2146.

135. Chen X.S., Kurre U., Jenkins N.A., Copeland N.G., Funk C.D. cDNA cloning, expression, mutagenesis of C-terminal isoleucine, genomic structure, and chromosomal localizations of murine 12-lipoxygenases // J. Biol. Chem. 1994. V. 269. P. 13979-13987.

136. Watanabe T., Medina J.F., Haeggstrom J.Z., Radmark O., Samuelsson B. Molecular cloning of a 12-lipoxygenase cDNA from rat brain // Eur. J. Biochem. 1993. V. 212. P. 605-612.

137. Berger M., Schwarz K., Thiele H., Reimann I., Huth A., Borngraber S., Kuhn H., Thiele B.J. Simultaneous expression of leukocyte-type 12-lipoxygenase and reticulocyte-type 15-lipoxygenase in rabbits // J. Mol. Biol. 1998. V. 278. P. 935-948.

138. Sun D., Funk C.D. Disruption of 12/15-lipoxygenase expression in peritoneal macrophages. Enhanced utilization of the 5-lipoxygenase pathway and diminished oxidation of low density lipoprotein // J. Biol. Chem. 1996. V. 271. P. 24055-24062.

139. Chen X.S., Sheller J.R., Johnson E.N., Funk C.D. Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase gene // Nature. 1994. V. 372. P. 179-182.

140. Johnson E.N., Brass L.F., Funk C.D. Increased platelet sensitivity to ADP in mice lacking platelet-type 12-lipoxygenase // Proc. Natl. Acad. Sci. USA. 1998. V. 95. P. 3100-3105.

141. Poeckel D., Zemski Berry K.A., Murphy R.C., Funk C.D. Dual 12/15- and 5-lipoxygenase deficiency in macrophages alters arachidonic acid metabolism and attenuates peritonitis and atherosclerosis in ApoE knock-out mice // J. Biol. Chem. 2009. V. 284. P. 21077-21089.

142. Porta H., Rocha-Sosa M. Plant lipoxygenases. Physiological and molecular features // Plant Physiol. 2002. V. 130. P. 15-21.

143. Feussner I., Wasternack C., Kindl H., Kuhn H. Lipoxygenase-catalyzed oxygenation of storage lipids is implicated in lipid mobilization during germination // Proc. Natl. Acad. Sci. USA. 1995. V. 92. P. 11849-11853.

144. Bousquet J.F., Thimann K.V. Lipid peroxidation forms ethylene from 1-aminocyclopropane-1-carboxylic acid and may operate in leaf senescence // Proc. Natl. Acad. Sci. USA. 1984. V. 81. P. 1724-1727.

145. He Y., Fukushige H., Hildebrand D.F., Gan S. Evidence supporting a role of jasmonic acid in arabidopsis leaf senescence // Plant Physiol. 2002. V. 128. P. 876-884.

146. Chen G., Hackett R., Walker D., Taylor A., Lin Z., Grierson D. Identification of a specific isoform of tomato lipoxygenase (TomloxC) involved in the generation of fatty acid-derived flavor compounds // Plant Physiol. 2004. V. 136. P. 2641-2651.

147. Ridolfi M., Terenziani S., Patumi M., Fontanazza G. Characterization of the lipoxygenases in some olive cultivars and determination of their role in volatile compounds formation // J. Agric. Food Chem. 2002. V. 50. P. 835-839.

148. Song W.C., Brash A.R. Investigation of the allene oxide pathway in the coral Plexaura homomalla: Formation of novel ketols and isomers of prostaglandin A2 from 15-hydroxyeicosatetraenoic acid // Arch. Biochem. Biophys. 1991. V. 290. P. 427-435.

149. Aparoy P., Reddy R.N., Guruprasad L., Reddy M.R., Reddanna P. Homology modeling of 5-lipoxygenase and hints for better inhibitor design // J. Comput. Aided Mol. Des. 2008. V. 22. P. 611-619.

150. Di Venere A., Horn T., Stehling S., Mei G., Masgrau L., González-Lafont A., Kühn H., Ivanov I. Role of Arg403 for thermostability and catalytic activity of rabbit 12/15-lipoxygenase // Biochim. Biophys. Acta. 2013. V. 1831. P. 1079-1088.

151. Di Venere A., Nicolai E., Ivanov I., Dainese E., Adel S., Angelucci B.C., Kuhn H., Maccarrone M., Mei G. Probing conformational changes in lipoxygenases upon membrane binding: Fine-tuning by the active site inhibitor ETYA // Biochim. Biophys. Acta. 2014. V. 1841. P. 1-10.


For citation:


Ivanov I.V., Groza N.V., Myagkova G.I., Kühn Kh. Structural biology of lipoxygenases: current knowledge and further development. Fine Chemical Technologies. 2014;9(4):3-26. (In Russ.)

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