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EcoSal Plus

Domain 4:

Synthesis and Processing of Macromolecules

Undecaprenyl Phosphate Synthesis

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  • Authors: Thierry TouzÉ1, and Dominique Mengin-Lecreulx2
  • Editor: James M. Slauch4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Université Paris-Sud, CNRS, UMR 8619, Laboratoire Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, Bâtiment 430, F-91405 Orsay Cedex, France; 2: Université Paris-Sud, CNRS, UMR 8619, Laboratoire Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, Bâtiment 430, F-91405 Orsay Cedex, France; 4: The Schoold of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL
  • Received 05 September 2007 Accepted 10 December 2007 Published 12 February 2008
  • Address correspondence to Thierry TouzÉ thierry.touze@u-psud.fr.
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  • Abstract:

    Undecaprenyl phosphate (C55-P) is an essential 55-carbon long-chain isoprene lipidinvolved in the biogenesis of bacterial cell wall carbohydrate polymers: peptidoglycan, O antigen, teichoic acids, and other cell surface polymers. It functions as a lipid carrier that allows the traffic of sugar intermediates across the plasma membrane, towards the periplasm,where the polymerization of the different cellwall components occurs. At the end of these processes, the lipid is released in a pyrophosphate form (C55-PP). C55-P arises from the dephosphorylation of C55-PP, which itself originates from either a recycling event or a synthesis. In , the formation of C55-PP is catalyzed by the essential UppS synthase, a soluble cis-prenyltransferase, whichadds eight isoprene units ontofarnesyl pyrophosphate. Severalapo- and halo-UppSthree-dimensional structures have provided a high level of understanding of this enzymatic step. The following dephosphorylationstep is required before the lipid carrier can accept a sugar unit at the cytoplasmic face of the membrane. Four integralmembrane proteins have been shown to catalyzethis reaction in E. coli:BacA and three members of the PAP2 super-family:YbjG, LpxT, and PgpB. None of these enzymes is essential,but the simultaneous inactivation of , , and genes gave rise to a lethal phenotype, raising the question of the relevance of such a redundancy of activity. It was alsorecently shown that LpxTcatalyzes the specific transfer of the phosphate group arising from C55-PP to the lipidA moiety of lipopolysaccharides, leading to a lipid-A 1-diphosphate form whichaccounts for one-third of the total lipidA in wild-type cells. The active sites of LpxT, PgpB,andYbjG were shown to face the periplasm, suggesting that PAP2 enzymes arerather involved in C55-PP recycling. These recent discoveries have opened the way to the elucidation of the functional and structural characterization of these different phosphatases.

  • Citation: TouzÉ T, Mengin-Lecreulx D. 2008. Undecaprenyl Phosphate Synthesis, EcoSal Plus 2008; doi:10.1128/ecosalplus.4.7.1.7

Key Concept Ranking

Bacterial Proteins
0.4873384
Cell Wall Components
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Bacterial Cell Wall
0.45779547
Integral Membrane Proteins
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References

1. van Heijenoort J. 1996. Murein synthesis, p 1025–1034. In Neidhardt FC, Curtiss R III, Ingraham JL, Lin ECC, Low KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, and Umbarger HE (ed), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed. ASM Press, Washington, DC.
2. van Heijenoort J. 2001. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat Prod Rep 18:503–519. [PubMed][CrossRef]
3. Raetz CRH. 1996. Bacterial lipopolysaccharides: a remarkable family of bioactive macroamphiphiles, p 1035–1063. In Neidhardt FC, Curtiss R III, Ingraham JL, Lin ECC, Low KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, and Umbarger HE (ed), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed., vol. 1. ASM Press, Washington, DC.
4. Kennedy EP. 1996. Membrane-derived oligosaccharides (periplasmic beta-D-glucans) of Escherichia coli, p 1064–1071. In Neidhardt FC, Curtiss R III, Ingraham JL, Lin ECC, Low KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, and Umbarger HE (ed), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed., vol. 1. ASM Press, Washington, DC.
5. Rick PD, Silver RP. 1996. Enterobacterial common antigen and capsular polysaccharides, p 104–122. In Neidhardt FC, Curtiss R III, Ingraham JL, Lin ECC, Low KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, and Umbarger HE (ed), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed., vol. 1. ASM Press, Washington, DC.
6. Chaykin S, Law J, Phillips AH, Tchen TT, Bloch K. 1958. Phosphorylated intermediates in the synthesis of squalene. Proc Natl Acad Sci USA 44:998–1004. [PubMed][CrossRef]
7. Wang KC, Ohnuma S. 2000. Isoprenyl diphosphate synthases. Biochim Biophys Acta 1529:33–48.[PubMed]
8. Chen AP, Chang SY, Lin YC, Sun YS, Chen CT, Wang AH, Liang PH. 2005. Substrate and product specificities of cis-type undecaprenyl pyrophosphate synthase. Biochem J 386:169–176. [PubMed][CrossRef]
9. Ogura K, Koyama T. 1998. Enzymatic aspects of isoprenoid chain elongation. Chem Rev 98:1263–1276. [PubMed][CrossRef]
10. Allen CM. 1985. Purification and characterization of undecaprenylpyrophosphate synthetase. Methods Enzymol 110:281–299. [PubMed][CrossRef]
11. Fujisaki S, Nishino T, Katsuki H. 1986. Isoprenoid synthesis in Escherichia coli. Separation and partial purification of four enzymes involved in the synthesis. J Biochem (Tokyo) 99:1327–1337.
12. Pan JJ, Chiou ST, Liang PH. 2000. Product distribution and pre-steady-state kinetic analysis of Escherichia coli undecaprenyl pyrophosphate synthase reaction. Biochemistry 39:10936–10942. [PubMed][CrossRef]
13. Liang PH, Ko TP, Wang AH. 2002. Structure, mechanism and function of prenyltransferases. Eur J Biochem 269:3339–3354. [PubMed][CrossRef]
14. Tarshis LC, Yan M, Poulter CD, Sacchettini JC. 1994. Crystal structure of recombinant farnesyl diphosphate synthase at 2.6-Å resolution. Biochemistry 33:10871–10877. [PubMed][CrossRef]
15. Shimizu N, Koyama T, Ogura K. 1998. Molecular cloning, expression, and characterization of the genes encoding the two essential protein components of Micrococcus luteus B-P 26 hexaprenyl diphosphate synthase. J Bacteriol 180:1578–1581.[PubMed]
16. Raetz CR. 1975. Isolation of Escherichia coli mutants defective in enzymes of membrane lipid synthesis. Proc Natl Acad Sci USA 72:2274–2278. [PubMed][CrossRef]
17. Cunillera N, Arro M, Fores O, Manzano D, Ferrer A. 2000. Characterization of dehydrodolichyl diphosphate synthase of Arabidopsis thaliana, a key enzyme in dolichol biosynthesis. FEBS Lett 477:170–174. [PubMed][CrossRef]
18. Endo S, Zhang YW, Takahashi S, Koyama T. 2003. Identification of human dehydrodolichyl diphosphate synthase gene. Biochim Biophys Acta 1625:291–295.[PubMed]
19. Hemmi H, Yamashita S, Shimoyama T, Nakayama T, Nishino T. 2001. Cloning, expression, and characterization of cis-polyprenyl diphosphate synthase from the thermoacidophilic archaeon Sulfolobus acidocaldarius. J Bacteriol 183:401–404. [PubMed][CrossRef]
20. Schulbach MC, Brennan PJ, Crick DC. 2000. Identification of a short (C15) chain Z-isoprenyl diphosphate synthase and a homologous long (C50) chain isoprenyl diphosphate synthase in Mycobacterium tuberculosis. J Biol Chem 275:22876–22881. [PubMed][CrossRef]
21. Apfel CM, Takacs B, Fountoulakis M, Stieger M, Keck W. 1999. Use of genomics to identify bacterial undecaprenyl pyrophosphate synthetase: cloning, expression, and characterization of the essential uppS gene. J Bacteriol 181:483–492.[PubMed]
22. Kato J, Fujisaki S, Nakajima K, Nishimura Y, Sato M, Nakano A. 1999. The Escherichia coli homologue of yeast RER2, a key enzyme of dolichol synthesis, is essential for carrier lipid formation in bacterial cell wall synthesis. J Bacteriol 181:2733–2738.[PubMed]
23. Pan JJ, Yang LW, Liang PH. 2000. Effect of site-directed mutagenesis of the conserved aspartate and glutamate on Escherichia coli undecaprenyl pyrophosphate synthase catalysis. Biochemistry 39:13856–13861. [PubMed][CrossRef]
24. Fujihashi M, Zhang YW, Higuchi Y, Li XY, Koyama T, Miki K. 2001. Crystal structure of cis-prenyl chain elongating enzyme, undecaprenyl diphosphate synthase. Proc Natl Acad Sci USA 98:4337–4342. [PubMed][CrossRef]
25. Ko TP, Chen YK, Robinson H, Tsai PC, Gao YG, Chen AP, Wang AH, Liang PH. 2001. Mechanism of product chain length determination and the role of a flexible loop in Escherichia coli undecaprenyl-pyrophosphate synthase catalysis. J Biol Chem 276:47474–47482. [PubMed][CrossRef]
26. Kinoshita K, Sadanami K, Kidera A, Go N. 1999. Structural motif of phosphate-binding site common to various protein superfamilies: all-against-all structural comparison of protein-mononucleotide complexes. Protein Eng 12:11–14. [PubMed][CrossRef]
27. Fujikura K, Zhang YW, Yoshizaki H, Nishino T, Koyama T. 2000. Significance of Asn-77 and Trp-78 in the catalytic function of undecaprenyl diphosphate synthase of Micrococcus luteus B-P 26. J Biochem (Tokyo) 128:917–922.
28. Kharel Y, Zhang YW, Fujihashi M, Miki K, Koyama T. 2001. Identification of significant residues for homoallylic substrate binding of Micrococcus luteus B-P 26 undecaprenyl diphosphate synthase. J Biol Chem 276:28459–28464. [PubMed][CrossRef]
29. Chang SY, Ko TP, Chen AP, Wang AH, Liang PH. 2004. Substrate binding mode and reaction mechanism of undecaprenyl pyrophosphate synthase deduced from crystallographic studies. Protein Sci 13:971–978. [PubMed][CrossRef]
30. Chang SY, Ko TP, Liang PH, Wang AH. 2003. Catalytic mechanism revealed by the crystal structure of undecaprenyl pyrophosphate synthase in complex with sulfate, magnesium, and triton. J Biol Chem 278:29298–29307. [PubMed][CrossRef]
31. Guo RT, Ko TP, Chen AP, Kuo CJ, Wang AH, Liang PH. 2005. Crystal structures of undecaprenyl pyrophosphate synthase in complex with magnesium, isopentenyl pyrophosphate, and farnesyl thiopyrophosphate: roles of the metal ion and conserved residues in catalysis. J Biol Chem 280:20762–20774. [PubMed][CrossRef]
32. Chang SY, Chen YK, Wang AH, Liang PH. 2003. Identification of the active conformation and the importance of length of the flexible loop 72–83 in regulating the conformational change of undecaprenyl pyrophosphate synthase. Biochemistry 42:14452–14459. [PubMed][CrossRef]
33. Chen YH, Chen AP, Chen CT, Wang AH, Liang PH. 2002. Probing the conformational change of Escherichia coli undecaprenyl pyrophosphate synthase during catalysis using an inhibitor and tryptophan mutants. J Biol Chem 277:7369–7376. [PubMed][CrossRef]
34. Takahashi S, Koyama T. 2006. Structure and function of cis-prenyl chain elongating enzymes. Chem Rec 6:194–205. [PubMed][CrossRef]
35. Bukhtiyarov YE, Shabalin YA, Kulaev IS. 1993. Solubilization and characterization of dehydrodolichyl diphosphate synthase from the yeast Saccharomyces carlsbergensis. J Biochem (Tokyo) 113:721–728.
36. Tarshis LC, Proteau PJ, Kellogg BA, Sacchettini JC, Poulter CD. 1996. Regulation of product chain length by isoprenyl diphosphate synthases. Proc Natl Acad Sci USA 93:15018–15023. [PubMed][CrossRef]
37. Wang K, Ohnuma S. 1999. Chain-length determination mechanism of isoprenyl diphosphate synthases and implications for molecular evolution. Trends Biochem Sci 24:445–451. [PubMed][CrossRef]
38. Sato M, Fujisaki S, Sato K, Nishimura Y, Nakano A. 2001. Yeast Saccharomyces cerevisiae has two cis-prenyltransferases with different properties and localizations. Implication for their distinct physiological roles in dolichol synthesis. Genes Cells 6:495–506. [PubMed][CrossRef]
39. Sato M, Sato K, Nishikawa S, Hirata A, Kato J, Nakano A. 1999. The yeast RER2 gene, identified by endoplasmic reticulum protein localization mutations, encodes cis-prenyltransferase, a key enzyme in dolichol synthesis. Mol Cell Biol 19:471–483.[PubMed]
40. Kharel Y, Takahashi S, Yamashita S, Koyama T. 2006. Manipulation of prenyl chain length determination mechanism of cis-prenyltransferases. FEBS J 273:647–657. [PubMed][CrossRef]
41. Siewert G, Strominger JL. 1967. Bacitracin: an inhibitor of the dephosphorylation of lipid pyrophosphate, an intermediate in the biosynthesis of the peptidoglycan of bacterial cell walls. Proc Natl Acad Sci USA 57:767–773. [PubMed][CrossRef]
42. Harkness RE, Braun V. 1989. Colicin M inhibits peptidoglycan biosynthesis by interfering with lipid carrier recycling. J Biol Chem 264:6177–6182.[PubMed]
43. Harkness RE, Braun V. 1989. Inhibition of lipopolysaccharide O-antigen synthesis by colicin M. J Biol Chem 264:14716–14722.[PubMed]
44. El Ghachi M, Bouhss A, Barreteau H, Touze T, Auger G, Blanot D, Mengin-Lecreulx D. 2006. Colicin M exerts its bacteriolytic effect via enzymatic degradation of undecaprenyl phosphate-linked peptidoglycan precursors. J Biol Chem 281:22761–22772. [PubMed][CrossRef]
45. Goldman R, Strominger JL. 1972. Purification and properties of C55-isoprenylpyrophosphate phosphatase from Micrococcus lysodeikticus. J Biol Chem 247:5116–5122.[PubMed]
46. El Ghachi M, Bouhss A, Blanot D, Mengin-Lecreulx D. 2004. The bacA gene of Escherichia coli encodes an undecaprenyl pyrophosphate phosphatase activity. J Biol Chem 279:30106–30113. [PubMed][CrossRef]
47. El Ghachi M, Derbise A, Bouhss A, Mengin-Lecreulx D. 2005. Identification of multiple genes encoding membrane proteins with undecaprenyl pyrophosphate phosphatase (UppP) activity in Escherichia coli. J Biol Chem 280:18689–18695. [PubMed][CrossRef]
48. Toscano WA Jr, Storm DR. 1982. Bacitracin. Pharmacol Ther 16:199–210. [PubMed][CrossRef]
49. Cain BD, Norton PJ, Eubanks W, Nick HS, Allen CM. 1993. Amplification of the bacA gene confers bacitracin resistance to Escherichia coli. J Bacteriol 175:3784–3789.[PubMed]
50. Chalker AF, Ingraham KA, Lunsford RD, Bryant AP, Bryant J, Wallis NG, Broskey JP, Pearson SC, Holmes DJ. 2000. The bacA gene, which determines bacitracin susceptibility in Streptococcus pneumoniae and Staphylococcus aureus, is also required for virulence. Microbiology 146:1547–1553.[PubMed]
51. Podlesek Z, Comino A, Herzog-Velikonja B, Zgur-Bertok D, Komel R, Grabnar M. 1995. Bacillus licheniformis bacitracin-resistance ABC transporter: relationship to mammalian multidrug resistance. Mol Microbiol 16:969–976. [PubMed][CrossRef]
52. Bernard R, Joseph P, Guiseppi A, Chippaux M, Denizot F. 2003. YtsCD and YwoA, two independent systems that confer bacitracin resistance to Bacillus subtilis. FEMS Microbiol Lett 228:93–97. [PubMed][CrossRef]
53. Mascher T, Margulis NG, Wang T, Ye RW, Helmann JD. 2003. Cell wall stress responses in Bacillus subtilis: the regulatory network of the bacitracin stimulon. Mol Microbiol 50:1591–1604. [PubMed][CrossRef]
54. Ohki, Tateno R, Giyanto K, Masuyama W, Moriya S, Kobayashi K, Ogasawara N. 2003. The BceRS two-component regulatory system induces expression of the bacitracin transporter, BceAB, in Bacillus subtilis. Mol Microbiol 49:1135–1144. [PubMed][CrossRef]
55. Ohki R, Tateno K, Okada Y, Okajima H, Asai K, Sadaie Y, Murata M, Aiso T. 2003. A bacitracin-resistant Bacillus subtilis gene encodes a homologue of the membrane-spanning subunit of the Bacillus licheniformis ABC transporter. J Bacteriol 185:51–59. [PubMed][CrossRef]
56. Harel YM, Bailone A, Bibi E. 1999. Resistance to bacitracin as modulated by an Escherichia coli homologue of the bacitracin ABC transporter BcrC subunit from Bacillus licheniformis. J Bacteriol 181:6176–6178.[PubMed]
57. Bernard R, El Ghachi M, Mengin-Lecreulx D, Chippaux M, Denizot F. 2005. BcrC from Bacillus subtilis acts as an undecaprenyl pyrophosphate phosphatase in bacitracin resistance. J Biol Chem 280:28852–28857. [PubMed][CrossRef]
58. Touzé, T, Tran AX, Hankins JV, Mengin-Lecreulx D, Trent MS. 2008. Periplasmic phosphorylation of lipid A is linked to the synthesis of undecaprenyl phosphate. Mol Microbiol 67:264–277.[PubMed]
59. Raetz CR, Whitfield C. 2002. Lipopolysaccharide endotoxins. Annu Rev Biochem 71:635–700. [PubMed][CrossRef]
60. Raetz CR, Reynolds CM, Trent MS, Bishop RE. 2007. Lipid A modification systems in gram-negative bacteria. Annu Rev Biochem 76:295–329. [PubMed][CrossRef]
61. Chang G, Roth CB. 2001. Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science 293:1793–1800. [PubMed][CrossRef]
62. Doerrler WT, Reedy MC, Raetz CR. 2001. An Escherichia coli mutant defective in lipid export. J Biol Chem 276:11461–11464. [PubMed][CrossRef]
63. Stukey J, Carman GM. 1997. Identification of a novel phosphatase sequence motif. Protein Sci 6:469–472.[PubMed]
64. Ishikawa K, Mihara Y, Gondoh K, Suzuki E, Asano Y. 2000. X-ray structures of a novel acid phosphatase from Escherichia blattae and its complex with the transition-state analog molybdate. EMBO J 19:2412–2423. [PubMed][CrossRef]
65. Dillon DA, Wu WI, Riedel B, Wissing JB, Dowhan W, Carman GM. 1996. The Escherichia coli pgpB gene encodes for a diacylglycerol pyrophosphate phosphatase activity. J Biol Chem 271:30548–30553. [PubMed][CrossRef]
66. Funk CR, Zimniak L, Dowhan W. 1992. The pgpA and pgpB genes of Escherichia coli are not essential: evidence for a third phosphatidylglycerophosphate phosphatase. J Bacteriol 174:205–213.[PubMed]
67. Tatar LD, Marolda CL, Polischuk AN, van Leeuwen D, Valvano MA. 2007. An Escherichia coli undecaprenyl-pyrophosphate phosphatase implicated in undecaprenyl phosphate recycling. Microbiology 153:2518–2529. [PubMed][CrossRef]
68. McCloskey MA, Troy FA. 1980. Paramagnetic isoprenoid carrier lipids. 1. Chemical synthesis and incorporation into model membranes. Biochemistry 19:2056–2060. [PubMed][CrossRef]
69. McCloskey MA, Troy FA. 1980. Paramagnetic isoprenoid carrier lipids. 2. Dispersion and dynamics in lipid membranes. Biochemistry 19:2061–2066. [PubMed][CrossRef]
70. Thaller MC, Schippa S, Rossolini GM. 1998. Conserved sequence motifs among bacterial, eukaryotic, and archaeal phosphatases that define a new phosphohydrolase superfamily. Protein Sci 7:1647–1652. [PubMed][CrossRef]
71. Neuwald AF. 1997. An unexpected structural relationship between integral membrane phosphatases and soluble haloperoxidases. Protein Sci 6:1764–1767. [PubMed][CrossRef]
72. Messerschmidt A, Wever R. 1996. X-ray structure of a vanadium-containing enzyme: chloroperoxidase from the fungus Curvularia inaequalis. Proc Natl Acad Sci USA 93:392–396. [PubMed][CrossRef]
73. Hemrika W, Renirie R, Dekker HL, Barnett P, Wever R. 1997. From phosphatases to vanadium peroxidases: a similar architecture of the active site. Proc Natl Acad Sci USA 94:2145–2149. [PubMed][CrossRef]
74. Littlechild J, Garcia-Rodriguez E, Dalby A, Isupov M. 2002. Structural and functional comparisons between vanadium haloperoxidase and acid phosphatase enzymes. J Mol Recognit 15:291–296. [PubMed][CrossRef]
75. Ghosh A, Shieh JJ, Pan CJ, Chou JY. 2004. Histidine 167 is the phosphate acceptor in glucose-6-phosphatase-beta forming a phosphohistidine enzyme intermediate during catalysis. J Biol Chem 279:12479–12483. [PubMed][CrossRef]
76. Ghosh A, Shieh JJ, Pan CJ, Sun MS, Chou JY. 2002. The catalytic center of glucose-6-phosphatase. HIS176 is the nucleophile forming the phosphohistidine-enzyme intermediate during catalysis. J Biol Chem 277:32837–32842. [PubMed][CrossRef]
77. Sarli S, Nicoletti M, Schippa S, Del Chierico F, Santapaola D, Valenti P, Berlutti F. 2005. Ala160 and His116 residues are involved in activity and specificity of apyrase, an ATP-hydrolysing enzyme produced by enteroinvasive Escherichia coli. Microbiology 151:2853–2860. [PubMed][CrossRef]
78. Vincent JB, Crowder MW, Averill BA. 1992. Hydrolysis of phosphate monoesters: a biological problem with multiple chemical solutions. Trends Biochem Sci 17:105–110. [PubMed][CrossRef]
79. Huitema K, van den Dikkenberg J, Brouwers JF, Holthuis JC. 2004. Identification of a family of animal sphingomyelin synthases. EMBO J 23:33–44. [PubMed][CrossRef]
80. Pyne S, Long JS, Ktistakis NT, Pyne NJ. 2005. Lipid phosphate phosphatases and lipid phosphate signalling. Biochem Soc Trans 33:1370–1374. [PubMed][CrossRef]
81. Higashi Y, Strominger JL, Sweeley CC. 1970. Biosynthesis of the peptidoglycan of bacterial cell walls. XXI. Isolation of free C55-isoprenoid alcohol and of lipid intermediates in peptidoglycan synthesis from Staphylococcus aureus. J Biol Chem 245:3697–3702.[PubMed]
82. Kalin JR, Allen CM, Jr. 1979. Characterization of undecaprenol kinase from Lactobacillus plantarum. Biochim Biophys Acta 574:112–122.[PubMed]
83. Sandermann H, Strominger JL. 1974. C55-isoprenoid alcohol phosphokinase: an enzyme soluble in organic solvents. Methods Enzymol 32:439–446. [PubMed][CrossRef]
84. Sandermann H Jr, Strominger JL. 1971. C55-isoprenoid alcohol phosphokinase: an extremely hydrophobic protein from the bacterial membrane. Proc Natl Acad Sci USA 68:2441–2443. [PubMed][CrossRef]
85. Sandermann H Jr, Strominger JL. 1972. Purification and properties of C55-isoprenoid alcohol phosphokinase from Staphylococcus aureus. J Biol Chem 247:5123–5131.[PubMed]
86. Gough DP, Kirby AL, Richards JB, Hemming FW. 1970. The characterization of undecaprenol of Lactobacillus plantarum. Biochem J 118:167–170.[PubMed]
87. Thorne KJ, Kodicek E. 1966. The structure of bactoprenol, a lipid formed by lactobacilli from mevalonic acid. Biochem J 99:123–127.[PubMed]
88. Umbreit JN, Stone KJ, Strominger JL. 1972. Isolation of polyisoprenyl alcohols from Streptococcus faecalis. J Bacteriol 112:1302–1305.[PubMed]
89. Vilim A, Woods MC, Carroll KK. 1973. Polyprenols of Listeria monocytogenes. Can J Biochem 51:939–941.[PubMed]
90. Lis M, Kuramitsu HK. 2003. The stress-responsive dgk gene from Streptococcus mutans encodes a putative undecaprenol kinase activity. Infect Immun 71:1938–1943. [PubMed][CrossRef]
91. Bohnenberger E, Sandermann H, Jr. 1979. Diglyceride kinase from Escherichia coli. Purification in organic solvent and some properties of the enzyme. Eur J Biochem 94:401–407. [PubMed][CrossRef]
92. van Dam V, Sijbrandi R, Kol M, Swiezewska E, de Kruijff B, Breukink E. 2007. Transmembrane transport of peptidoglycan precursors across model and bacterial membranes. Mol Microbiol 64:1105–1114. [PubMed][CrossRef]
93. Rick PD, Barr K, Sankaran K, Kajimura J, Rush JS, Waechter CJ. 2003. Evidence that the wzxE gene of Escherichia coli K-12 encodes a protein involved in the transbilayer movement of a trisaccharide-lipid intermediate in the assembly of enterobacterial common antigen. J Biol Chem 278:16534–16542. [PubMed][CrossRef]
94. Rush JS, van Leyen K, Ouerfelli O, Wolucka B, Waechter CJ. 1998. Transbilayer movement of Glc-P-dolichol and its function as a glucosyl donor: protein-mediated transport of a water-soluble analog into sealed ER vesicles from pig brain. Glycobiology 8:1195–1205. [PubMed][CrossRef]
95. Zhou Z, White KA, Polissi A, Georgopoulos C, Raetz CR. 1998. Function of Escherichia coli MsbA, an essential ABC family transporter, in lipid A and phospholipid biosynthesis. J Biol Chem 273:12466–12475. [PubMed][CrossRef]
96. Zhou GP, Troy FA II. 2003. Characterization by NMR and molecular modeling of the binding of polyisoprenols and polyisoprenyl recognition sequence peptides: 3D structure of the complexes reveals sites of specific interactions. Glycobiology 13:51–71. [PubMed][CrossRef]
97. Zhou GP, Troy FA II. 2005. NMR study of the preferred membrane orientation of polyisoprenols (dolichol) and the impact of their complex with polyisoprenyl recognition sequence peptides on membrane structure. Glycobiology 15:347–359. [PubMed][CrossRef]
98. Fiedler W, Rotering H. 1988. Properties of Escherichia coli mutants lacking membrane-derived oligosaccharides. J Biol Chem 263:14684–14689.[PubMed]
99. Pollock TJ, Thorne L, Yamazaki M, Mikolajczak MJ, Armentrout RW. 1994. Mechanism of bacitracin resistance in gram-negative bacteria that synthesize exopolysaccharides. J Bacteriol 176:6229–6237.[PubMed]
100. Anselme C, Vallier A, Balmand S, Fauvarque MO, Heddi A. 2006. Host PGRP gene expression and bacterial release in endosymbiosis of the weevil Sitophilus zeamais. Appl Environ Microbiol 72:6766–6772. [PubMed][CrossRef]
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/content/journal/ecosalplus/10.1128/ecosalplus.4.7.1.7
2008-02-12
2017-07-26

Abstract:

Undecaprenyl phosphate (C55-P) is an essential 55-carbon long-chain isoprene lipidinvolved in the biogenesis of bacterial cell wall carbohydrate polymers: peptidoglycan, O antigen, teichoic acids, and other cell surface polymers. It functions as a lipid carrier that allows the traffic of sugar intermediates across the plasma membrane, towards the periplasm,where the polymerization of the different cellwall components occurs. At the end of these processes, the lipid is released in a pyrophosphate form (C55-PP). C55-P arises from the dephosphorylation of C55-PP, which itself originates from either a recycling event or a synthesis. In , the formation of C55-PP is catalyzed by the essential UppS synthase, a soluble cis-prenyltransferase, whichadds eight isoprene units ontofarnesyl pyrophosphate. Severalapo- and halo-UppSthree-dimensional structures have provided a high level of understanding of this enzymatic step. The following dephosphorylationstep is required before the lipid carrier can accept a sugar unit at the cytoplasmic face of the membrane. Four integralmembrane proteins have been shown to catalyzethis reaction in E. coli:BacA and three members of the PAP2 super-family:YbjG, LpxT, and PgpB. None of these enzymes is essential,but the simultaneous inactivation of , , and genes gave rise to a lethal phenotype, raising the question of the relevance of such a redundancy of activity. It was alsorecently shown that LpxTcatalyzes the specific transfer of the phosphate group arising from C55-PP to the lipidA moiety of lipopolysaccharides, leading to a lipid-A 1-diphosphate form whichaccounts for one-third of the total lipidA in wild-type cells. The active sites of LpxT, PgpB,andYbjG were shown to face the periplasm, suggesting that PAP2 enzymes arerather involved in C55-PP recycling. These recent discoveries have opened the way to the elucidation of the functional and structural characterization of these different phosphatases.

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Figures

Image of Figure 1
Figure 1

Here, the newly formed double bond is in a (Z) configuration. “A” designates the prenyltransferase residue that plays the role of the C-PP C-2 proton acceptor before this proton is transferred to the leaving pyrophosphate group. IPP, isopentenyl pyrophosphate; R, allylic substrate carbon chain.

Citation: TouzÉ T, Mengin-Lecreulx D. 2008. Undecaprenyl Phosphate Synthesis, EcoSal Plus 2008; doi:10.1128/ecosalplus.4.7.1.7
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Image of Figure 2
Figure 2

The synthesis of C-P involves two enzymatic steps: first, the undecaprenyl pyrophosphate synthase (UppS) catalyzes the sequential condensation of -C-PP with eight molecules of C-PP, yielding C-PP; thereafter, C-PP is dephosphorylated. OP, phosphate group; OPP, pyrophosphate group.

Citation: TouzÉ T, Mengin-Lecreulx D. 2008. Undecaprenyl Phosphate Synthesis, EcoSal Plus 2008; doi:10.1128/ecosalplus.4.7.1.7
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Image of Figure 3
Figure 3

The figure was prepared with the atomic coordinates (1JP3) deposited in the Protein Data Bank by Ko et al. in 2001 ( 25 ). One dimer is shown by red α-helices and green β-strands, and the other monomer is shown by purple α-helices and blue β-strands. The region from residue 72 to 83 was not visible in the electron density map, suggestive of a flexible loop; a dotted line was added in one monomer to resolve the localization of the corresponding region. The hydrophobic cleft at the molecular surface of the molecule is indicated by arrows. This figure was prepared using PyMol.

Citation: TouzÉ T, Mengin-Lecreulx D. 2008. Undecaprenyl Phosphate Synthesis, EcoSal Plus 2008; doi:10.1128/ecosalplus.4.7.1.7
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Image of Figure 4
Figure 4

The ribbon diagram of the protein in two different orientations is shown close up, centered at the substrate binding site. The figure was prepared with the atomic coordinates 1X06 deposited in the Protein Data Bank by Guo et al. in 2005 ( 31 ). It corresponds to the structure of UppS in a complex with FsPP, C-PP, and Mg. In this structure, densities for C-PP were low, which dissuaded the authors from modeling the corresponding molecule; therefore, only the FsPP substrate is shown. For clarity, FsPP is represented as either line (up) or sphere (down) models. The side chains of residues interacting with FsPP are shown as line models; C, O N, P, and S atoms are in green, red, blue, orange, and yellow, respectively. The flexible loop that becomes visible upon allylic substrate binding is colored in red.

Citation: TouzÉ T, Mengin-Lecreulx D. 2008. Undecaprenyl Phosphate Synthesis, EcoSal Plus 2008; doi:10.1128/ecosalplus.4.7.1.7
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Image of Figure 5
Figure 5

Only the regions which encompass the three conserved motifs, designated C1, C2, and C3, are presented here. The corresponding sequences of five integral membrane proteins, the (EC) PAP2 C-PP phosphatases (PgpB, YbjG, and YeiU), YwoA (BS-YwoA), and BcrC (BL-BcrC), along with the soluble globular protein nonspecific acid phosphatase (EB-NSAP) are aligned. The first line shows the PAP2 consensus identified by Carman and Stuckey in 1997 ( 63 ). The consensus residues, as well as additional conserved residues, are indicated in red; the asterisks and the plus signs point out identical and similar residues, respectively. The line above the NSAP sequence indicates the location of α-helices, designated H, based on the three-dimensional structure of the protein ( 64 ). The black lines below the sequences indicate the locations of the predicted transmembrane segments (T3 to T6) in PAP2 C-PP phosphatases. Unaligned residues are indicated by lowercase letters.

Citation: TouzÉ T, Mengin-Lecreulx D. 2008. Undecaprenyl Phosphate Synthesis, EcoSal Plus 2008; doi:10.1128/ecosalplus.4.7.1.7
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Image of Figure 6
Figure 6

C-PP, the precursor of the lipid carrier, is de novo synthesized in the cytoplasm, from which it is partitioned into the inner side of the cytoplasmic membrane, but C-PP is also released at the outer side of the membrane after the transfer of the glycan moieties to the acceptor polymers. In the proposed model, BacA ensures the dephosphorylation of the de novo-synthesized C-PP on the cytosolic side of the membrane whereas the PAP2 phosphatase enzymes, YeiU, YbjG, and probably PgpB, are involved exclusively in the recycling of C-PP on the outer side of the membrane. YeiU was shown to establish a link between C-P biogenesis and lipid A structure modification by transferring the distal phosphate group from C-PP to lipid A, generating free lipid carrier and lipid A 1-diphosphate (lipid A 1-diP) species. Because of its involvement in the modification of the lipid A structure, YeiU was renamed LpxT. As indicated by question marks, it is yet unknown how C-P and the C-PP-sugar complex are translocated from one leaflet of the membrane to the other.

Citation: TouzÉ T, Mengin-Lecreulx D. 2008. Undecaprenyl Phosphate Synthesis, EcoSal Plus 2008; doi:10.1128/ecosalplus.4.7.1.7
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Image of Figure 7
Figure 7

(A) The ribbon diagram of the central region encompassing residues 91 to 210 is shown; the entire molecule comprises 249 amino acids. The three catalytic domains, C1, C2, and C3, are localized at the end of four long α-helices, and they are colored in red, grey, and pink, respectively. The catalytic triad residues and the molybdate ion are shown in line models; Mo, C, N, and O atoms are in blue, green, dark blue, and red, respectively. (B) Detailed interactions of molybdate with the catalytic triad and three other consensus residues. The dotted yellow lines indicate polar contacts. N-ter, N terminus; C-ter, C terminus.

Citation: TouzÉ T, Mengin-Lecreulx D. 2008. Undecaprenyl Phosphate Synthesis, EcoSal Plus 2008; doi:10.1128/ecosalplus.4.7.1.7
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Image of Figure 8
Figure 8

N-ter, N terminus; C-ter, C terminus; T1 to T6, transmembrane segments 1 to 6; L1 to L5, loops.

Citation: TouzÉ T, Mengin-Lecreulx D. 2008. Undecaprenyl Phosphate Synthesis, EcoSal Plus 2008; doi:10.1128/ecosalplus.4.7.1.7
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