Structural, mechanistic and regulatory studies of serine palmitoyltransferase

Biochemical Society Transactions

Volumn 40, Issue 3, 2012, Pages 547-554

  Lowther, Jonathan ^a   Naismith, James H ^b   Dunn, Teresa M ^c   Campopiano, Dominic J ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b UNIVERSITY OF ST ANDREWS   (United Kingdom)

^c UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES   (United States)

Author keywords

External aldimine; Pyridoxal 5 phosphate (PLP); Quinonoid intermediate; Serine palmitoyltransferase (SPT); Sphingolipid; Sphingomonas sp

Indexed keywords

BACTERIAL ENZYME; PYRIDOXAL 5 PHOSPHATE; SERINE PALMITOYLTRANSFERASE;

AMINO ACID SEQUENCE; BACTERIAL MEMBRANE; BACTERIAL SURVIVAL; CONFERENCE PAPER; CRYSTAL STRUCTURE; CYTOTOXICITY; ENDOPLASMIC RETICULUM; ENZYME ACTIVITY; ENZYME METABOLISM; ENZYME PHOSPHORYLATION; ENZYME STRUCTURE; NONHUMAN; POLYMERIZATION; PRIORITY JOURNAL; SPHINGOBACTERIUM MULTIVORUM; SPHINGOMONAS PAUCIMOBILIS;

ANIMALS; BACTERIA; ENZYME INHIBITORS; HUMANS; ISOENZYMES; MODELS, MOLECULAR; PROTEIN SUBUNITS; SERINE C-PALMITOYLTRANSFERASE;

BACTERIA (MICROORGANISMS); EUKARYOTA; MAMMALIA; PROKARYOTA; SPHINGOMONAS;

EID: 84861518863     PISSN: 03005127     EISSN: 14708752     Source Type: Journal    
DOI: 10.1042/BST20110769     Document Type: Conference Paper

References (53)

1. Fahy, E., Cotter, D., Sud, M. and Subramaniam, S. (2011) Lipid classification, structures and tools. Biochim. Biophys. Acta 1811, 637-647
2. Merrill, Jr, A.H. (2011) Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics. Chem. Rev. 111, 6387-6422
3. Ternes, P., Wobbe, T., Schwarz, M., Albrecht, S., Feussner, K., Riezman, I., Cregg, J.M., Heinz, E., Riezman, H., Feussner, I. and Warnecke, D. (2011) Two pathways of sphingolipid biosynthesis are separated in the yeast Pichia pastoris. J. Biol. Chem. 286, 11401-11414
4. Kawahara, K., Seydel, U., Matsuura, M., Danbara, H., Rietschel, E.T. and Zahringer, U. (1991) Chemical structure of glycosphingolipids isolated from Sphingomonas paucimobilis. FEBS Lett. 292, 107-110
5. Mun, J., Onorato, A., Nichols, F.C., Morton, M.D., Saleh, A.I., Welzel, M. and Smith, M.B. (2007) Structural confirmation of the dihydrosphinganine and fatty acid constituents of the dental pathogen Porphyromonas gingivalis. Org. Biomol. Chem. 5, 3826-3833 (Pubitemid 350115425)
6. Hanada, K. (2003) Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim. Biophys. Acta 1632, 16-30
7. Yim, M.S., Yau, Y.C., Matlow, A., So, J.S., Zou, J., Flemming, C.A., Schraft, H. and Leung, K.T. (2010) A novel selective growth medium-PCR assay to isolate and detect Sphingomonas in environmental samples. J. Microbiol. Methods 82, 19-27
8. Eliot, A.C. and Kirsch, J.F. (2004) Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations. Annu. Rev. Biochem. 73, 383-415 (Pubitemid 39050374)
9. Alexeev, D., Alexeeva, M., Baxter, R.L., Campopiano, D.J., Webster, S.P. and Sawyer, L. (1998) The crystal structure of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent, acyl-CoA-condensing enzyme. J. Mol. Biol. 284, 401-419 (Pubitemid 28542462)
10. Astner, I., Schulze, J.O., van den Heuvel, J., Jahn, D., Schubert, W.D. and Heinz, D.W. (2005) Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans. EMBO J. 24, 3166-3177 (Pubitemid 41348692)
11. Schmidt, A., Sivaraman, J., Li, Y., Larocque, R., Barbosa, J.A., Smith, C., Matte, A., Schrag, J.D. and Cygler, M. (2001) Three-dimensional structure of 2-amino-3-ketobutyrate CoA ligase from Escherichia coli complexed with a PLP-substrate intermediate: inferred reaction mechanism. Biochemistry 40, 5151-5160 (Pubitemid 32373997)
12. Jahan, N., Potter, J.A., Sheikh, M.A., Botting, C.H., Shirran, S.L., Westwood, N.J. and Taylor, G.L. (2009) Insights into the biosynthesis of the Vibrio cholerae major autoinducer CAI-1 from the crystal structure of the PLP-dependent enzyme CqsA. J. Mol. Biol. 392, 763-773
13. Kelly, R.C., Bolitho, M.E., Higgins, D.A., Lu, W., Ng, W.L., Jeffrey, P.D., Rabinowitz, J.D., Semmelhack, M.F., Hughson, F.M. and Bassler, B.L. (2009) The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA. Nat. Chem. Biol. 5, 891-895
14. Ikushiro, H., Hayashi, H. and Kagamiyama, H. (2001) A water-soluble homodimeric serine palmitoyltransferase from Sphingomonas paucimobilis EY2395T strain: purification, characterization, cloning, and overproduction. J. Biol. Chem. 276, 18249-18256
15. Yard, B.A., Carter, L.G., Johnson, K.A., Overton, I.M., Dorward, M., Liu, H., McMahon, S.A., Oke, M., Puech, D., Barton, G.J. et al. (2007) The structure of serine palmitoyltransferase; gateway to sphingolipid biosynthesis. J. Mol. Biol. 370, 870-886 (Pubitemid 46899061)
16. Shiraiwa, Y., Ikushiro, H. and Hayashi, H. (2009) Multifunctional role of His159 in the catalytic reaction of serine palmitoyltransferase. J. Biol. Chem. 284, 15487-15495
17. Raman, M.C., Johnson, K.A., Yard, B.A., Lowther, J., Carter, L.G., Naismith, J.H. and Campopiano, D.J. (2009) The external aldimine form of serine palmitoyltransferase: structural, kinetic, and spectroscopic analysis of the wild-type enzyme and HSAN1 mutant mimics. J. Biol. Chem. 284, 17328-17339
18. Lowther, J., Charmier, G., Raman, M.C., Ikushiro, H., Hayashi, H. and Campopiano, D.J. (2011) Role of a conserved arginine residue during catalysis in serine palmitoyltransferase. FEBS Lett. 585, 1729-1734
19. Ikushiro, H., Islam, M.M., Okamoto, A., Hoseki, J., Murakawa, T., Fujii, S., Miyahara, I. and Hayashi, H. (2009) Structural insights into the enzymatic mechanism of serine palmitoyltransferase from Sphingobacterium multivorum. J. Biochem. 146, 549-562
20. Raman, M.C., Johnson, K.A., Clarke, D.J., Naismith, J.H. and Campopiano, D.J. (2010) The serine palmitoyltransferase from Sphingomonas wittichii RW1: an interesting link to an unusual acyl carrier protein. Biopolymers 93, 811-822
21. Geiger, O., Gonzalez-Silva, N., Lopez-Lara, I.M. and Sohlenkamp, C. (2010) Amino acid-containing membrane lipids in bacteria. Prog. Lipid Res. 49, 46-60
22. Ikushiro, H., Islam, M.M., Tojo, H. and Hayashi, H. (2007) Molecular characterization of membrane-associated soluble serine palmitoyltransferases from Sphingobacterium multivorum and Bdellovibrio stolpii. J. Bacteriol. 189, 5749-5761 (Pubitemid 47206421)
23. Gable, K., Slife, H., Bacikova, D., Monaghan, E. and Dunn, T.M. (2000) Tsc3p is an 80-amino acid protein associated with serine palmitoyltransferase and required for optimal enzyme activity. J. Biol. Chem. 275, 7597-7603 (Pubitemid 30159659)
24. Hanada, K., Hara, T. and Nishijima, M. (2000) Purification of the serine palmitoyltransferase complex responsible for sphingoid base synthesis by using affinity peptide chromatography techniques. J. Biol. Chem. 275, 8409-8415 (Pubitemid 30180184)
25. Snell, E.E., Dimari, S.J. and Brady, R.N. (1970) Biosynthesis of sphingosine and dihydrosphingosine by cell-free systems from Hansenula ciferri. Chem. Phys. Lipids 5, 116-138
26. Williams, R.D., Wang, E. and Merrill, Jr, A.H. (1984) Enzymology of long-chain base synthesis by liver: characterization of serine palmitoyltransferase in rat liver microsomes. Arch. Biochem. Biophys. 228, 282-291 (Pubitemid 14175782)
27. An, D., Na, C., Bielawski, J., Hannun, Y.A. and Kasper, D.L. (2011) Membrane sphingolipids as essential molecular signals for Bacteroides survival in the intestine. Proc. Natl. Acad. Sci. U.S.A. 108 (Suppl. 1), 4666-4671
28. Lowther, J., Yard, B.A., Johnson, K.A., Carter, L.G., Bhat, V.T., Raman, M.C., Clarke, D.J., Ramakers, B., McMahon, S.A., Naismith, J.H. and Campopiano, D.J. (2010) Inhibition of the PLP-dependent enzyme serine palmitoyltransferase by cycloserine: evidence for a novel decarboxylative mechanism of inactivation. Mol. Biosyst. 6, 1682-1693
29. Buede, R., Rinker-Schaffer, C., Pinto, W.J., Lester, R.L. and Dickson, R.C. (1991) Cloning and characterization of LCB1, a Saccharomyces gene required for biosynthesis of the long-chain base component of sphingolipids. J. Bacteriol. 173, 4325-4332
30. Hanada, K., Hara, T., Nishijima, M., Kuge, O., Dickson, R.C. and Nagiec, M.M. (1997) A mammalian homolog of the yeast LCB1 encodes a component of serine palmitoyltransferase, the enzyme catalyzing the first step in sphingolipid synthesis. J. Biol. Chem. 272, 32108-32114 (Pubitemid 28011882)
31. Hornemann, T., Richard, S., Rutti, M.F., Wei, Y. and von Eckardstein, A. (2006) Cloning and initial characterization of a new subunit for mammalian serine-palmitoyltransferase. J. Biol. Chem. 281, 37275-37281 (Pubitemid 46042031)
32. Nagiec, M.M., Baltisberger, J.A., Wells, G.B., Lester, R.L. and Dickson, R.C. (1994) The LCB2 gene of Saccharomyces and the related LCB1 gene encode subunits of serine palmitoyltransferase, the initial enzyme in sphingolipid synthesis. Proc. Natl. Acad. Sci. U.S.A. 91, 7899-7902 (Pubitemid 24253852)
33. Nagiec, M.M., Lester, R.L. and Dickson, R.C. (1996) Sphingolipid synthesis: identification and characterization of mammalian cDNAs encoding the Lcb2 subunit of serine palmitoyltransferase. Gene 177, 237-241 (Pubitemid 26370788)
34. Weiss, B. and Stoffel, W. (1997) Human and murine serine-palmitoyl-CoA transferase: cloning, expression and characterization of the key enzyme in sphingolipid synthesis. Eur. J. Biochem. 249, 239-247 (Pubitemid 27432617)
35. Zhao, C., Beeler, T. and Dunn, T. (1994) Suppressors of the Ca2+ -sensitive yeast mutant (csg2) identify genes involved in sphingolipid biosynthesis: cloning and characterization of SCS1, a gene required for serine palmitoyltransferase activity. J. Biol. Chem. 269, 21480-21488
36. Han, G., Gable, K., Yan, L., Natarajan, M., Krishnamurthy, J., Gupta, S.D., Borovitskaya, A., Harmon, J.M. and Dunn, T.M. (2004) The topology of the Lcb1p subunit of yeast serine palmitoyltransferase. J. Biol. Chem. 279, 53707-53716 (Pubitemid 40051879)
37. Bejaoui, K., Wu, C., Scheffler, M.D., Haan, G., Ashby, P., Wu, L., de Jong, P. and Brown, Jr, R.H. (2001) SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nat. Genet. 27, 261-262 (Pubitemid 32201845)
38. Gable, K., Han, G., Monaghan, E., Bacikova, D., Natarajan, M., Williams, R. and Dunn, T.M. (2002) Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase. J. Biol. Chem. 277, 10194-10200 (Pubitemid 34968133)
39. Rotthier, A., Auer-Grumbach, M., Janssens, K., Baets, J., Penno, A., Almeida-Souza, L., Van Hoof, K., Jacobs, A., De Vriendt, E., Schlotter-Weigel, B. et al. (2010) Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I. Am. J. Hum. Genet. 87, 513-522
40. Gable, K., Gupta, S.D., Han, G., Niranjanakumari, S., Harmon, J.M. and Dunn, T.M. (2010) A disease-causing mutation in the active site of serine palmitoyltransferase causes catalytic promiscuity. J. Biol. Chem. 285, 22846-22852
41. Penno, A., Reilly, M.M., Houlden, H., Laura, M., Rentsch, K., Niederkofler, V., Stoeckli, E.T., Nicholson, G., Eichler, F., Brown, Jr, R.H. et al. (2010) Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids. J. Biol. Chem. 285, 11178-11187
42. Garofalo, K., Penno, A., Schmidt, B.P., Lee, H.J., Frosch, M.P., von Eckardstein, A., Brown, R.H., Hornemann, T. and Eichler, F.S. (2011) Oral l-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. J. Clin. Invest. 121, 4735-4745
43. Zitomer, N.C., Mitchell, T., Voss, K.A., Bondy, G.S., Pruett, S.T., Garnier-Amblard, E.C., Liebeskind, L.S., Park, H., Wang, E., Sullards, M.C. et al. (2009) Ceramide synthase inhibition by fumonisin B1 causes accumulation of 1-deoxysphinganine: a novel category of bioactive 1-deoxysphingoid bases and 1-deoxydihydroceramides biosynthesized by mammalian cell lines and animals. J. Biol. Chem. 284, 4786-4795
44. Huang, S., Cheng, T.Y., Young, D.C., Layre, E., Madigan, C.A., Shires, J., Cerundolo, V., Altman, J.D. and Moody, D.B. (2011) Discovery of deoxyceramides and diacylglycerols as CD1b scaffold lipids among diverse groove-blocking lipids of the human CD1 system. Proc. Natl. Acad. Sci. U.S.A. 108, 19335-19340
45. Dietrich, C.R., Han, G., Chen, M., Berg, R.H., Dunn, T.M. and Cahoon, E.B. (2008) Loss-of-function mutations and inducible RNAi suppression of Arabidopsis LCB2 genes reveal the critical role of sphingolipids in gametophytic and sporophytic cell viability. Plant J. 54, 284-298 (Pubitemid 351503124)
46. Hojjati, M.R., Li, Z. and Jiang, X.C. (2005) Serine palmitoyl-CoA transferase (SPT) deficiency and sphingolipid levels in mice. Biochim. Biophys. Acta 1737, 44-51 (Pubitemid 41550382)
47. Han, G., Gupta, S.D., Gable, K., Niranjanakumari, S., Moitra, P., Eichler, F., Brown, Jr, R.H., Harmon, J.M. and Dunn, T.M. (2009) Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities. Proc. Natl. Acad. Sci. U.S.A. 106, 8186-8191
48. Breslow, D.K., Collins, S.R., Bodenmiller, B., Aebersold, R., Simons, K., Shevchenko, A., Ejsing, C.S. and Weissman, J.S. (2010) Orm family proteins mediate sphingolipid homeostasis. Nature 463, 1048-1053
49. Han, S., Lone, M.A., Schneiter, R. and Chang, A. (2010) Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control. Proc. Natl. Acad. Sci. U.S.A. 107, 5851-5856
50. Hjelmqvist, L., Tuson, M., Marfany, G., Herrero, E., Balcells, S. and Gonzalez-Duarte, R. (2002) ORMDL proteins are a conserved new family of endoplasmic reticulum membrane proteins. Genome Biol. 3, RESEARCH0027
51. Roelants, F.M., Breslow, D.K., Muir, A., Weissman, J.S. and Thorner, J. (2011) Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 108, 19222-19227
52. Hornemann, T., Wei, Y. and von Eckardstein, A. (2007) Is the mammalian serine palmitoyltransferase a high-molecular-mass complex? Biochem. J. 405, 157-164 (Pubitemid 46999936)
53. Bourquin, F., Capitani, G. and Grutter, M.G. (2011) PLP-dependent enzymes as entry and exit gates of sphingolipid metabolism. Protein Sci. 20, 1492-1508