1w1o Citations

Structures of Michaelis and product complexes of plant cytokinin dehydrogenase: implications for flavoenzyme catalysis.

J. Mol. Biol. 341 1237-49 (2004)
Related entries: 1w1s, 1w1r, 1w1q

Cited: 27 times
EuropePMC logo PMID: 15321719

Abstract

Cytokinins form a diverse class of compounds that are essential for plant growth. Cytokinin dehydrogenase has a major role in the control of the levels of these plant hormones by catalysing their irreversible oxidation. The crystal structure of Zea mays cytokinin dehydrogenase displays the same two-domain topology of the flavoenzymes of the vanillyl-alcohol oxidase family but its active site cannot be related to that of any other family member. The X-ray analysis reveals a bipartite architecture of the catalytic centre, which consists of a funnel-shaped region on the protein surface and an internal cavity lined by the flavin ring. A pore with diameter of about 4A connects the two active-site regions. Snapshots of two critical steps along the reaction cycle were obtained through the structural analysis of the complexes with a slowly reacting substrate and the reaction product, which correspond to the states immediately before (Michaelis complex) and after (product complex) oxidation has taken place. The substrate displays a "plug-into-socket" binding mode that seals the catalytic site and precisely positions the carbon atom undergoing oxidation in close contact with the reactive locus of the flavin. A polarising H-bond between the substrate amine group and an Asp-Glu pair may facilitate oxidation. Substrate to product conversion results in small atomic movements, which lead to a planar conformation of the reaction product allowing double-bond conjugation. These features in the mechanism of amine recognition and oxidation differ from those observed in other flavin-dependent amine oxidases.

Reviews citing this publication (7)

  1. Cytokinin oxidase is key enzyme of cytokinin degradation. Avalbaev AM, Somov KA, Yuldashev RA, Shakirova FM. Biochemistry (Mosc) 77 1354-1361 (2012)
  2. Evolution of cytokinin biosynthesis and degradation. Frébort I, Kowalska M, Hluska T, Frébortová J, Galuszka P. J Exp Bot 62 2431-2452 (2011)
  3. What's in a covalent bond? On the role and formation of covalently bound flavin cofactors. Heuts DP, Scrutton NS, McIntire WS, Fraaije MW. FEBS J 276 3405-3427 (2009)
  4. The growing VAO flavoprotein family. Leferink NG, Heuts DP, Fraaije MW, van Berkel WJ. Arch Biochem Biophys 474 292-301 (2008)
  5. Kinetin--a multiactive molecule. Barciszewski J, Massino F, Clark BF. Int J Biol Macromol 40 182-192 (2007)
  6. To be or not to be an oxidase: challenging the oxygen reactivity of flavoenzymes. Mattevi A. Trends Biochem Sci 31 276-283 (2006)
  7. New insights into the biology of cytokinin degradation. Werner T, Köllmer I, Bartrina I, Holst K, Schmülling T. Plant Biol (Stuttg) 8 371-381 (2006)

Articles citing this publication (20)

  1. ThermoFAD, a Thermofluor-adapted flavin ad hoc detection system for protein folding and ligand binding. Forneris F, Orru R, Bonivento D, Chiarelli LR, Mattevi A. FEBS J 276 2833-2840 (2009)
  2. A concerted mechanism for berberine bridge enzyme. Winkler A, Lyskowski A, Riedl S, Puhl M, Kutchan TM, Macheroux P, Gruber K. Nat Chem Biol 4 739-741 (2008)
  3. Structural basis for benzothiazinone-mediated killing of Mycobacterium tuberculosis. Neres J, Pojer F, Molteni E, Chiarelli LR, Dhar N, Boy-Röttger S, Buroni S, Fullam E, Degiacomi G, Lucarelli AP, Read RJ, Zanoni G, Edmondson DE, De Rossi E, Pasca MR, McKinney JD, Dyson PJ, Riccardi G, Mattevi A, Cole ST, Binda C. Sci Transl Med 4 150ra121 (2012)
  4. Tissue localization of cytokinin dehydrogenase in maize: possible involvement of quinone species generated from plant phenolics by other enzymatic systems in the catalytic reaction. Galuszka P, Frébortová J, Luhová L, Bilyeu KD, English JT, Frébort I. Plant Cell Physiol 46 716-728 (2005)
  5. Subcellular localization and biochemical comparison of cytosolic and secreted cytokinin dehydrogenase enzymes from maize. Smehilová M, Galuszka P, Bilyeu KD, Jaworek P, Kowalska M, Sebela M, Sedlárová M, English JT, Frébort I. J Exp Bot 60 2701-2712 (2009)
  6. Crystal structure of 6-hydroxy-D-nicotine oxidase from Arthrobacter nicotinovorans. Koetter JW, Schulz GE. J Mol Biol 352 418-428 (2005)
  7. Crystal structure analysis of free and substrate-bound 6-hydroxy-L-nicotine oxidase from Arthrobacter nicotinovorans. Kachalova GS, Bourenkov GP, Mengesdorf T, Schenk S, Maun HR, Burghammer M, Riekel C, Decker K, Bartunik HD. J Mol Biol 396 785-799 (2010)
  8. Structural characterization of glucooligosaccharide oxidase from Acremonium strictum. Lee MH, Lai WL, Lin SF, Hsu CS, Liaw SH, Tsai YC. Appl Environ Microbiol 71 8881-8887 (2005)
  9. High-level expression and characterization of Zea mays cytokinin oxidase/dehydrogenase in Yarrowia lipolytica. Kopecný D, Pethe C, Sebela M, Houba-Hérin N, Madzak C, Majira A, Laloue M. Biochimie 87 1011-1022 (2005)
  10. Combinatorially selected defense peptides protect plant roots from pathogen infection. Fang ZD, Laskey JG, Huang S, Bilyeu KD, Morris RO, Schmidt FJ, English JT. Proc Natl Acad Sci U S A 103 18444-18449 (2006)
  11. Degradation of cytokinins by maize cytokinin dehydrogenase is mediated by free radicals generated by enzymatic oxidation of natural benzoxazinones. Frébortová J, Novák O, Frébort I, Jorda R. Plant J 61 467-481 (2010)
  12. Kinetic and chemical analyses of the cytokinin dehydrogenase-catalysed reaction: correlations with the crystal structure. Popelková H, Fraaije MW, Novák O, Frébortová J, Bilyeu KD, Frébort I. Biochem J 398 113-124 (2006)
  13. Molecular, phylogenetic and comparative genomic analysis of the cytokinin oxidase/dehydrogenase gene family in the Poaceae. Mameaux S, Cockram J, Thiel T, Steuernagel B, Stein N, Taudien S, Jack P, Werner P, Gray JC, Greenland AJ, Powell W. Plant Biotechnol J 10 67-82 (2012)
  14. Mechanism-based inhibitors of cytokinin oxidase/dehydrogenase attack FAD cofactor. Kopecný D, Sebela M, Briozzo P, Spíchal L, Houba-Hérin N, Masek V, Joly N, Madzak C, Anzenbacher P, Laloue M. J Mol Biol 380 886-899 (2008)
  15. Crystal structure of Arabidopsis thaliana cytokinin dehydrogenase. Bae E, Bingman CA, Bitto E, Aceti DJ, Phillips GN. Proteins 70 303-306 (2008)
  16. Probing cytokinin homeostasis in Arabidopsis thaliana by constitutively overexpressing two forms of the maize cytokinin oxidase/dehydrogenase 1 gene Kopecny D, Tarkowski P, Majira A, Bouchez-Mahiout I, Nogue F, Lauriere M, Sandberg G, Laloue M, Houba-Herin N. Plant Sci 171 114-122 (2006)
  17. Brassinin oxidase mediated transformation of the phytoalexin brassinin: structure of the elusive co-product, deuterium isotope effect and stereoselectivity. Pedras MS, Minic Z, Sarma-Mamillapalle VK. Bioorg Med Chem 19 1390-1399 (2011)
  18. Implementation of pseudoreceptor-based pharmacophore queries in the prediction of probable protein targets: explorations in the protein structural profile of Zea mays. Kumar SP, Jha PC, Pandya HA, Jasrai YT. Mol Biosyst 10 1833-1844 (2014)
  19. Biochemical Characterization of Putative Adenylate Dimethylallyltransferase and Cytokinin Dehydrogenase from Nostoc sp. PCC 7120. Frébortová J, Greplová M, Seidl MF, Heyl A, Frébort I. PLoS One 10 e0138468 (2015)
  20. Kinetic and structural investigation of the cytokinin oxidase/dehydrogenase active site. Kopečný D, Končitíková R, Popelka H, Briozzo P, Vigouroux A, Kopečná M, Zalabák D, Šebela M, Skopalová J, Frébort I, Moréra S. FEBS J 283 361-377 (2016)