Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Structural Basis for Recognition of L-lysine, L-ornithine, and L-2,4-diamino Butyric Acid by Lysine Cyclodeaminase

  • Min, Kyungjin (Department of Chemistry, College of Natural Sciences, Seoul National University) ;
  • Yoon, Hye-Jin (Department of Chemistry, College of Natural Sciences, Seoul National University) ;
  • Matsuura, Atsushi (Department of Pharmacy, Dongguk University) ;
  • Kim, Yong Hwan (School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST)) ;
  • Lee, Hyung Ho (Department of Chemistry, College of Natural Sciences, Seoul National University)
  • Received : 2017.11.22
  • Accepted : 2018.01.08
  • Published : 2018.04.30
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Abstract

L-pipecolic acid is a non-protein amino acid commonly found in plants, animals, and microorganisms. It is a well-known precursor to numerous microbial secondary metabolites and pharmaceuticals, including anticancer agents, immunosuppressants, and several antibiotics. Lysine cyclodeaminase (LCD) catalyzes ${\beta}$-deamination of L-lysine into L-pipecolic acid using ${\beta}$-nicotinamide adenine dinucleotide as a cofactor. Expression of a human homolog of LCD, ${\mu}$-crystallin, is elevated in prostate cancer patients. To understand the structural features and catalytic mechanisms of LCD, we determined the crystal structures of Streptomyces pristinaespiralis LCD (SpLCD) in (i) a binary complex with $NAD^+$, (ii) a ternary complex with $NAD^+$ and L-pipecolic acid, (iii) a ternary complex with $NAD^+$ and L-proline, and (iv) a ternary complex with $NAD^+$ and L-2,4-diamino butyric acid. The overall structure of SpLCD was similar to that of ornithine cyclodeaminase from Pseudomonas putida. In addition, SpLCD recognized L-lysine, L-ornithine, and L-2,4-diamino butyric acid despite differences in the active site, including differences in hydrogen bonding by Asp236, which corresponds with Asp228 from Pseudomonas putida ornithine cyclodeaminase. The substrate binding pocket of SpLCD allowed substrates smaller than lysine to bind, thus enabling binding to ornithine and L-2,4-diamino butyric acid. Our structural and biochemical data facilitate a detailed understanding of substrate and product recognition, thus providing evidence for a reaction mechanism for SpLCD. The proposed mechanism is unusual in that $NAD^+$ is initially converted into NADH and then reverted back into $NAD^+$ at a late stage of the reaction.

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References

  1. Adams, P.D., Grosse-Kunstleve, R.W., Hung, L.W., Ioerger, T.R., McCoy, A.J., Moriarty, N.W., Read, R.J., Sacchettini, J.C., Sauter, N.K., and Terwilliger, T.C. (2002). PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr. D Biol. Crystallogr. 58, 1948-1954. https://doi.org/10.1107/S0907444902016657
  2. Bis, D.M., Ban, Y.H., James, E.D., Alqahtani, N., Viswanathan, R., and Lane, A.L. (2015). Characterization of the nocardiopsin biosynthetic gene cluster reveals similarities to and differences from the rapamycin and FK-506 pathways. Chembiochem.16, 990-997. https://doi.org/10.1002/cbic.201500007
  3. Boger, D.L., Chen, J.-H., and Saionz, K.W. (1996). (-)-Sandramycin: total synthesis and characterization of DNA binding Properties. J. Am. Chem. Soc.118, 1629-1644. https://doi.org/10.1021/ja952799y
  4. Broquist, H.P. (1991). Lysine-pipecolic acid metabolic relationships in microbes and mammals. Annu. Rev. Nutr. 11, 435-448. https://doi.org/10.1146/annurev.nu.11.070191.002251
  5. Byun, S.M., Jeong, S.W., Cho, D.H., and Kim, Y.H. (2015). Optimized conversion of L-lysine to L-pipecolic acid using recombinant lysine cyclodeaminase from Streptomyces pristinaespiralis. Biotechnol. Biopoc. E.20, 73-78. https://doi.org/10.1007/s12257-014-0428-3
  6. Cheng, Z., Sun, L., He, J., and Gong, W. (2007). Crystal structure of human micro-crystallin complexed with NADPH. Protein Sci.16, 329-335.
  7. Choi, H., Min, K., Mikami, B., Yoon, H.J., and Lee, H.H. (2016). Structural and biochemical studies reveal a putative FtsZ recognition site on the Z-ring stabilizer ZapD. Mol. Cells 39, 814-820. https://doi.org/10.14348/molcells.2016.0202
  8. Couty, F. (1999). Asymmetric syntheses of pipecolic acid and derivatives. Amino Acids.16, 297-320. https://doi.org/10.1007/BF01388174
  9. Durzan, D.J. (1983). Plant nonprotein amino and imino acids: biological, biochemical, and toxicological properties. Gerald A. Rosenthal. The Quarterly Rev. Biol. 58, 260.
  10. Eichhorn, E., Roduit, J.-P., Shaw, N., Heinzmann, K., and Kiener, A. (1997). Preparation of (S)-piperazine-2-carboxylic acid, (R)-piperazine-2-carboxylic acid, and (S)-piperidine-2-carboxylic acid by kinetic resolution of the corresponding racemic carboxamides with stereoselective amidases in whole bacterial cells. Tetrahedron: Asymmetry. 8, 2533-2536. https://doi.org/10.1016/S0957-4166(97)00256-5
  11. Emsley, P., and Cowtan, K. (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-2132. https://doi.org/10.1107/S0907444904019158
  12. Frey, P.A. (1996) The Leloir pathway: a mechanistic imperative for three enzymes to change the stereochemical configuration of a single carbon in galactose. FASEB J. 10, 461-470. https://doi.org/10.1096/fasebj.10.4.8647345
  13. Fujii, T., Mukaihara, M., and Tsunekawa, H. (2002) Biotransformation of l-lysine to l-pipecolic acid catalyzed by l-lysine 6-aminotransferase and pyrroline-5-carboxylate reductase. Biosci. Biotechnol. Biochem. 66, 622-627. https://doi.org/10.1271/bbb.66.622
  14. Fujioka, S., and Sakurai, A. (1992) Effect of L-pipecolic acid on flowering in Lemna paucicostata and Lemna gibba. Plant Cell Physiol. 33, 419-426.
  15. Gallagher, D.T., Monbouquette, H.G., Schroder, I., Robinson, H., Holden, M.J., and Smith, N.N. (2004) Structure of alanine dehydrogenase from Archaeoglobus: active site analysis and relation to bacterial cyclodeaminases and mammalian mu crystallin. J. Mol. Biol. 342, 119-130. https://doi.org/10.1016/j.jmb.2004.06.090
  16. Garcia De La Torre, J., Huertas, M.L., and Carrasco, B. (2000) Calculation of hydrodynamic properties of globular proteins from their atomic-level structure. Biophys. J. 78, 719-730. https://doi.org/10.1016/S0006-3495(00)76630-6
  17. Garcia, P.F., Wendisch, P.P., and Wendisch, V.F. (2016). Engineering Corynebacterium glutamicum for fast production of l-lysine and lpipecolic acid. Appl. Microbiol. Biotechnol. 100, 8075-8090. https://doi.org/10.1007/s00253-016-7682-6
  18. Gatto, G.J., Jr., Boyne, M.T., 2nd, Kelleher, N.L., and Walsh, C.T. (2006). Biosynthesis of pipecolic acid by RapL, a lysine cyclodeaminase encoded in the rapamycin gene cluster. J. Am. Chem. Soc.128, 3838-3847. https://doi.org/10.1021/ja0587603
  19. Germann, U.A., Shlyakhter, D., Mason, V.S., Zelle, R.E., Duffy, J.P., Galullo, V., Armistead, D.M., Saunders, J.O., Boger, J., and Harding, M.W. (1997). Cellular and biochemical characterization of VX-710 as a chemosensitizer: reversal of P-glycoprotein-mediated multidrug resistance in vitro. Anticancer Drugs 8, 125-140. https://doi.org/10.1097/00001813-199702000-00004
  20. Goodman, J.L., Wang, S., Alam, S., Ruzicka, F.J., Frey, P.A. and Wedekind, J.E. (2004). Ornithine cyclodeaminase: structure, mechanism of action, and implications for the mu-crystallin family. Biochemistry 43, 13883-13891. https://doi.org/10.1021/bi048207i
  21. Gouesbet, G., Jebbar, M., Talibart, R., Bernard, T., and Blanco, C. (1994). Pipecolic acid is an osmoprotectant for Escherichia coli taken up by the general osmoporters ProU and ProP. Microbiology 140, 2415-2422. https://doi.org/10.1099/13500872-140-9-2415
  22. Graupner, M., and White, R.H. (2001). Methanococcus jannaschii generates L-proline by cyclization of L-ornithine. J. Bacteriol. 183, 5203-5205. https://doi.org/10.1128/JB.183.17.5203-5205.2001
  23. Gupta, R.N., and Spenser, I.D. (1969). Biosynthesis of the piperidine nucleus. The mode of incorporation of lysine into pipecolic acid and into piperidine alkaloids. J. Biol. Chem. 244, 88-94.
  24. He, M. (2006). Pipecolic acid in microbes: biosynthetic routes and enzymes. J. Ind. Microbiol. Biotechnol. 33, 401-407. https://doi.org/10.1007/s10295-006-0078-3
  25. Holm, L., and Rosenstrom, P. (2010). Dali server: conservation mapping in 3D. Nucleic Acids Res. 38, W545-549. https://doi.org/10.1093/nar/gkq366
  26. Hu, Y., Yang, X., Yin, D.H., Mahadevan, J., Kuczera, K., Schowen, R.L., and Borchardt, R.T. (2001). Computational characterization of substrate binding and catalysis in S-adenosylhomocysteine hydrolase. Biochemistry 40, 15143-15152. https://doi.org/10.1021/bi015690d
  27. Jin, X., and Geiger, J.H. (2003). Structures of NAD(+)- and NADH-bound 1-l-myo-inositol 1-phosphate synthase. Acta Crystallogr. D Biol. Crystallogr. 59, 1154-1164. https://doi.org/10.1107/S0907444903008205
  28. Kadouri-Puchot, C., and Comesse, S. (2005). Recent advances in asymmetric synthesis of pipecolic acid and derivatives. Amino Acids 29, 101-130. https://doi.org/10.1007/s00726-005-0193-x
  29. Krissinel, E. and Henrick, K. (2007). Inference of macromolecular assemblies from crystalline state. J.Mol.Biol. 372, 774-797. https://doi.org/10.1016/j.jmb.2007.05.022
  30. Lemire, A., and Charette, A.B. (2010). Stereoselective syntheses of lpipecolic acid and (2S,3S)-3-hydroxypipecolic acid from a chiral N-imino-2-phenyl-1,2-dihydropyridine intermediate. J. Org. Chem.75, 2077-2080. https://doi.org/10.1021/jo902527s
  31. Malinowska, K., Cavarretta, I.T., Susani, M., Wrulich, O.A., Uberall, F., Kenner, L., and Culig, Z. (2009). Identification of mu-crystallin as an androgen-regulated gene in human prostate cancer. Prostate 69, 1109-1118. https://doi.org/10.1002/pros.20956
  32. McCoy, A.J., Grosse-Kunstleve, R.W., Adams, P.D., Winn, M.D., Storoni, L.C., and Read, R.J. (2007). Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674. https://doi.org/10.1107/S0021889807021206
  33. Mihalik, S.J., Moser, H.W., Watkins, P.A., Danks, D.M., Poulos, A., and Rhead, W.J. (1989). Peroxisomal L-pipecolic acid oxidation is deficient in liver from zellweger syndrome patients. Pediatr. Res. 25, 548-552. https://doi.org/10.1203/00006450-198905000-00024
  34. Miller, D.L., and Rodwell, V.W. (1971). Metabolism of basic amino acids in Pseudomonas putida. Catabolism of lysine by cyclic and acyclic intermediates. J. Biol. Chem. 246, 2758-2764.
  35. Moulin, M., Deleu, C., Larher, F., and Bouchereau, A. (2006). The lysine-ketoglutarate reductase-saccharopine dehydrogenase is involved in the osmo-induced synthesis of pipecolic acid in rapeseed leaf tissues. Plant Physiol. Biochem. 44, 474-482. https://doi.org/10.1016/j.plaphy.2006.08.005
  36. Navarova, H., Bernsdorff, F., Doring, A.-C. and Zeier, J. (2012). Pipecolic acid, an endogenous mediator of defense amplification and priming, is a critical regulator of inducible plant immunity. Plant Cell 24, 5123-5141. https://doi.org/10.1105/tpc.112.103564
  37. Neshich, I.A.P., Kiyota, E., and Arruda, P. (2013). Genome-wide analysis of lysine catabolism in bacteria reveals new connections with osmotic stress resistance. ISME J.7, 2400-2410. https://doi.org/10.1038/ismej.2013.123
  38. Otwinowski, Z., and Minor, W. (1997). Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326.
  39. Palfi, G., and Dezsi, L. (1968). Pipecolic acid as an indicator of abnormal protein metabolism in diseased plants. Plant and Soil 29, 285-291. https://doi.org/10.1007/BF01348946
  40. Rao, V.V., and Chang, Y.F. (1992). Assay for L-pipecolate oxidase activity in human liver: detection of enzyme deficiency in hyperpipecolic acidaemia. Biochim. Biophys. Acta.1139, 189-195. https://doi.org/10.1016/0925-4439(92)90133-8
  41. Tani, Y., Miyake, R., and Mihara, H. (2015). Functional expression of l-lysine ${\alpha}$-oxidase from Scomber japonicus in Escherichia coli for onepot synthesis of l-pipecolic acid from dl-lysine. Appl. Microbiol. Biotechnol. 99, 5045-5054. https://doi.org/10.1007/s00253-014-6308-0
  42. Thompson, J.D., Gibson, T.J., Plewniak, F., Jeanmougin, F., and Higgins, D.G. (1997). The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 25, 4876-4882. https://doi.org/10.1093/nar/25.24.4876
  43. Tsotsou, G.E., and Barbirato, F. (2007). Biochemical characterisation of recombinant Streptomyces pristinaespiralis L-lysine cyclodeaminase. Biochimie 89, 591-604. https://doi.org/10.1016/j.biochi.2006.12.008
  44. Watanabe, L.A., Haranaka, S., Jose, B., Yoshida, M., Kato, T., Moriguchi, M., Soda, K. and Nishino, N. (2005). An efficient access to both enantiomers of pipecolic acid. Tetrahedron: Asymmetry 16, 903-908. https://doi.org/10.1016/j.tetasy.2005.01.017
  45. Wilkinson, T.J., Stehle, N.W. and Beak, P. (2000) Enantioselective syntheses of 2-Alkyl- and 2,6-dialkylpiperidine alkaloids: preparations of the hydrochlorides of (-)-coniine, (-)-solenopsin A, and (-)-dihydropinidine. Organic Lett. 2, 155-158. https://doi.org/10.1021/ol9912534
  46. Ying, H.X., Wang, J., and Chen, K.Q. (2015). Enhanced conversion of l-lysine to l-pipecolic acid using a recombinant Escherichia coli containing lysine cyclodeaminase as whole-cell biocatalyst. J. Mol. Catal. B-Enzym.117, 75-80. https://doi.org/10.1016/j.molcatb.2015.05.001
  47. Ying, H., Tao, S., Wang, J., Ma, W., Chen, K., Wang, X., and Ouyang, P. (2017a). Expanding metabolic pathway for de novo biosynthesis of the chiral pharmaceutical intermediate l-pipecolic acid in Escherichia coli. Microb. Cell Fact.16, 52. https://doi.org/10.1186/s12934-017-0666-0
  48. Ying, H., Wang, J., Shi, T., Zhao, Y., Wang, X., Ouyang, P., and Chen, K. (2017b). Studies of lysine cyclodeaminase from Streptomyces pristinaespiralis: Insights into the complex transition $NAD^+$ state. Biochem. Biophys. Res. Commun. S0006-291X, 32211-32218.
  49. Zacharius, R.M., Thompson, J.F., and Steward, F.C. (1954). The detection, isolation and identification of L(-)pipecolic acid in the nonprotein fraction of beans (Phascolus vulgaris)1,2. J. Am. Chem. Soc. 76, 2908-2912. https://doi.org/10.1021/ja01640a015

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