Skip to main content
SpringerLink
Log in

Lysine biosynthesis in bacteria: a metallodesuccinylase as a potential antimicrobial target

  • Minireview
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

In this review, we summarize the recent literature on dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) enzymes, with an emphasis on structure–function studies that provide insight into the catalytic mechanism. Crystallographic data have also provided insight into residues that might be involved in substrate and hence inhibitor recognition and binding. These data have led to the design and synthesis of several new DapE inhibitors, which are described along with what is known about how inhibitors interact with the active site of DapE enzymes, including the efficacy of a moderately strong DapE inhibitor.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

AAP:

Aminopeptidase from Vibrio proteolyticus (Aeromonas proteolytica)

CEPA:

2-Carboxyethylphosphonic acid

CPG2:

Carboxypeptidase G2 from Pseudomonas sp. strain RS-16

DapE:

dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase

EPR:

Electron paramagnetic resonance

EXAFS:

Extended X-ray absorption fine structure

l,l-SDAP:

N-Succinyl-l,l-diaminopimelic acid

LPA:

l-Leucine phosphonic acid

m-DAP:

meso-Diaminopimelate

MSPA:

5-Mercaptopentanoic acid

SDAP:

N-Succinyldiaminopimelic acid

References

  1. CfDCa Prevention (1995) MMWR Morb Mortal Wkly Rep 44:1–13

    Google Scholar 

  2. Howe RA, Bowker KE, Walsh TR, Feest TG, MacGowan AP (1998) Lancet 351:601–602

    Article  Google Scholar 

  3. Levy SB (1998) Sci Am 278:46–53

    Article  PubMed  CAS  Google Scholar 

  4. Chin J (1996) New Sci 152:32–35

    CAS  Google Scholar 

  5. Henery CM (2000) C&E News 78:41–58

    Google Scholar 

  6. Nemecek S (1997) Sci Am 276:38–39

    Article  PubMed  CAS  Google Scholar 

  7. Miller JB (2000) In: The pharmaceutical century: ten decades of drug discovery. American Chemical Society, Washington, pp 52–71

    Google Scholar 

  8. Lesney MS, Frey R (2000) In: The pharmaceutical century: ten decades of drug discovery. American Chemical Society, Washington, pp 110–129

    Google Scholar 

  9. Frey R, Lesney MS (2000) In: The pharmaceutical century: ten decades of drug discovery. American Chemical Society, Washington, pp 92–109

    Google Scholar 

  10. Tweedy BD, Lesney MS (2000) In: The pharmaceutical century: ten decades of drug discovery. American Chemical Society, Washington, pp 72–91

    Google Scholar 

  11. Snider DE, Raviglione M, Kochi A (1994) In: Bloom BR (ed) Global burden of tuberculosis. ASM Press, Washington, pp 3–11

    Google Scholar 

  12. Dolin PJ, Raviglione MC, Kochi A (1994) Bull WHO 72:213–220

    PubMed  CAS  Google Scholar 

  13. Raviglione MC, Snider DE, Kochi A (1995) JAMA 273:220–226

    Article  PubMed  CAS  Google Scholar 

  14. Teuber M (1999) Cell Mol Life Sci 56:755–763

    Article  PubMed  CAS  Google Scholar 

  15. Miller JR, Dunham S, Mochalkin I, Banotai C, Bowman M, Buist S, Dunkle B, Hanna D, Harwood HJ, Huband MD, Karnovsky A, Kuhn M, Limberakis C, Liu JY, Mehrens S, Mueller WT, Narasimhan L, Ogden A, Ohren J, Prasad JV, Shelly JA, Skerlos L, Sulavik M, Thomas VH, VanderRoest S, Wang L, Wang Z, Whitton A, Zhu T, Stover CK (2009) Proc Natl Acad Sci USA 106:1737–1742. doi:10.1073/pnas.0811275106

    Article  PubMed  CAS  Google Scholar 

  16. Scapin G, Blanchard JS (1998) Adv Enzymol 72:279–325

    PubMed  CAS  Google Scholar 

  17. Born TL, Blanchard JS (1999) Cur Opin Chem Biol 3:607–613

    Article  CAS  Google Scholar 

  18. Girodeau J-M, Agouridas C, Masson M, Pineau R, Le Goffic F (1986) J Med Chem 29:1023–1030

    Google Scholar 

  19. Cox RJ, Sutherland A, Vederas JC (2000) Bioorg Med Chem 8:843–871

    Article  PubMed  CAS  Google Scholar 

  20. Vederas JC (2006) Can J Chem 84:1197–1207

    Article  CAS  Google Scholar 

  21. Hutton CA, Perugini MA, Gerrard JA (2007) Mol Biosyst 3:458–465

    Article  PubMed  CAS  Google Scholar 

  22. Born TL, Zheng R, Blanchard JS (1998) Biochemistry 37:10478–10487

    Article  PubMed  CAS  Google Scholar 

  23. Karita M, Etterbeek ML, Forsyth MH, Tummuru MR, Blaser MJ (1997) Infect Immun 65:4158–4164

    PubMed  CAS  Google Scholar 

  24. Pavelka MS, Jacobs WR (1996) J Bacteriol 178:6496–6507

    PubMed  CAS  Google Scholar 

  25. Bouvier J, Richaud C, Higgins W, Bögler O, Stragier P (1992) J Bacteriol 174:5265–5271

    PubMed  CAS  Google Scholar 

  26. Fuchs TM, Schneider B, Krumbach K, Eggeling L, Gross R (2000) J Bacteriol 182:3626–3631

    Article  PubMed  CAS  Google Scholar 

  27. Shaw-Reid CA, McCormick MM, Sinskey AJ, Stephanopoulos G (1999) Appl Microbiol Biotechnol 51:325–333

    Article  PubMed  CAS  Google Scholar 

  28. Lin Y, Myhrman R, Schrag ML, Gelb MH (1988) J Biol Chem 263:1622–1627

    PubMed  CAS  Google Scholar 

  29. Gillner DM, Bienvenue DL, Nocek BP, Joachimiak A, Zachary V, Bennett B, Holz RC (2009) J Biol Inorg Chem 14:1–10

    Article  PubMed  CAS  Google Scholar 

  30. Barrett AJ, Rawlings ND, Woessner JF (eds) (1998) Handbook of proteolytic enzymes. Academic, London

    Google Scholar 

  31. Rowsell S, Pauptit RA, Tucker AD, Melton RG, Blow DM, Brick P (1997) Structure 5:337–347

    Article  PubMed  CAS  Google Scholar 

  32. Desmarais W, Bienvenue DL, Bzymek KP, Petsko GA, Ringe D, Holz RC (2006) J Biol Inorg Chem 11:398–408

    Article  PubMed  CAS  Google Scholar 

  33. Chevrier B, Schalk C, D’Orchymont H, Rondeau J-M, Moras D, Tarnus C (1994) Structure 2:283–291

    Article  PubMed  CAS  Google Scholar 

  34. Greenblatt HM, Almog O, Maras B, Spungin-Bialik A, Barra D, Blumberg S, Shoham G (1997) J Mol Biol 265:620–636

    Article  PubMed  CAS  Google Scholar 

  35. Bienvenue DL, Gilner DM, Davis RS, Bennett B, Holz RC (2003) Biochemistry 42:10756–10763

    Article  PubMed  CAS  Google Scholar 

  36. Cosper NJ, Bienvenue DL, Shokes JE, Gilner DM, Tsukamoto T, Scott R, Holz RC (2003) J Am Chem Soc 125:14654–14655

    Article  PubMed  CAS  Google Scholar 

  37. Davis R, Bienvenue D, Swierczek SI, Gilner DM, Rajagopal L, Bennett B, Holz RC (2006) J Biol Inorg Chem 11:206–216

    Article  PubMed  CAS  Google Scholar 

  38. Bennett B (2010) In: Hanson G, Berliner L (eds) Metals in biology. Biological magnetic resonance, vol 29. Springer, New York, pp 345–370

  39. Badger J, Sauder JM, Adams JM, Antonysamy S, Bain K, Bergseid MG, Buchanan SG, Buchanan MD, Batiyenko Y, Christopher JA, Emtage S, Eroshkina A, Feil I, Furlong EB, Gajiwala KS, Gao X, He D, Hendle J, Huber A, Hoda K, Kearins P, Kissinger C, Laubert B, Lewis HA, Lin J, Loomis K, Lorimer D, Louie G, Maletic M, Marsh CD, Miller I, Molinari J, Muller-Dieckmann HJ, Newman JM, Noland BW, Pagarigan B, Park F, Peat TS, Post KW, Radojicic S, Ramos A, Romero R, Rutter ME, Sanderson WE, Schwinn KD, Tresser J, Winhoven J, Wright TA, Wu L, Xu J, Harris TJ (2005) Proteins 60:787–796

    Article  PubMed  CAS  Google Scholar 

  40. Nocek BP, Gillner DM, Fan Y, Holz RC, Joachimiak A (2010) J Mol Biol 397:617–626. doi:10.1016/j.jmb.2010.01.062

    Article  PubMed  CAS  Google Scholar 

  41. Tyndall JDA, Nall T, Fairlie DP (2005) Chem Rev 105:973–999

    Article  PubMed  CAS  Google Scholar 

  42. Gillner DM, Armoush N, Holz RC, Becker D (2009) Bioorg Med Chem Lett 19:6350–6352

    Article  PubMed  CAS  Google Scholar 

  43. Vaněk V, Pícha J, Buděšínský M, Šanda M, Jiráček J, Holz RC, Hlaváček J (2010) Protein Pept Lett 17:405–409

    Article  PubMed  Google Scholar 

  44. Ustynyuk L, Bennett B, Edwards T, Holz RC (1999) Biochemistry 38:11433–11439

    Article  PubMed  CAS  Google Scholar 

  45. Stamper CC, Bienvenue DL, Moulin A, Bennett B, Ringe D, Petsko GA, Holz RC (2004) Biochemistry 43:9620–9628

    Article  PubMed  CAS  Google Scholar 

  46. Copik AJ, Swierczek SI, Lowther WT, D’souza VM, Matthews BW, Holz RC (2003) Biochemistry 42:6283–6292

    Article  PubMed  CAS  Google Scholar 

  47. Ye QZ, Xie SX, Ma ZQ, Huang M, Hanzlik RP (2006) Proc Natl Acad Sci USA 103:9470–9475

    Article  PubMed  CAS  Google Scholar 

  48. Holz RC (2002) Coord Chem Rev 232:5–26

    Article  CAS  Google Scholar 

  49. Stamper CC, Bennett B, Edwards T, Holz RC, Ringe D, Petsko GA (2001) Biochemistry 40:7035–7046

    Article  PubMed  CAS  Google Scholar 

  50. Sträter N, Lipscomb WN (1995) Biochemisty 34:9200–9210

    Article  Google Scholar 

  51. Jacobsen FE, Lewis JA, Cohen SM (2007) Chem Med Chem 2:152–171

    PubMed  CAS  Google Scholar 

  52. Uda NR, Creus M (2011) Bioinorg Chem Appl 2011:306465. doi:10.1155/2011/306465

    Article  PubMed  Google Scholar 

  53. Arfin SM, Kendall RL, Hall L, Weaver LH, Stewart AE, Matthews BW, Bradshaw RA (1995) Proc Natl Acad Sci USA 92:7714–7718

    Article  PubMed  CAS  Google Scholar 

  54. Ben-Bassat A, Bauer AK, Chang S-Y, Myambo K, Boosman A, Chang S (1987) J Bacteriol 169:751–757

    PubMed  CAS  Google Scholar 

  55. Ben-Bassat A, Bauer K (1987) Nature 326:315

    Article  Google Scholar 

  56. Chang S-Y, McGary EC, Chang S (1989) J Bacteriol 171:4071–4072

    PubMed  CAS  Google Scholar 

  57. Gonzales T, Robert-Baudouy J (1996) FEMS Microbiol Rev 18:319–344

    Article  PubMed  CAS  Google Scholar 

  58. Taylor A (1993) FASEB J 7:290–298

    PubMed  CAS  Google Scholar 

  59. Taylor A (1993) Trends Biochem Sci 18:167–172

    PubMed  CAS  Google Scholar 

  60. Taylor A (ed) (1996) Aminopeptidases. Landes, Austin

    Google Scholar 

Download references

Acknowledgments

This work was supported by the National Institutes of Health (R15 AI085559-01A1, R.C.H.).

Author information

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Loyola University-Chicago, 1068 W. Sheridan Rd., Chicago, IL, 60626, USA

    Danuta M. Gillner, Daniel P. Becker & Richard C. Holz

  2. Department of Chemistry, Silesian University of Technology, ul. Krzywoustego 4, 44-100, Gliwice, Poland

    Danuta M. Gillner

Authors
  1. Danuta M. Gillner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel P. Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard C. Holz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Danuta M. Gillner or Richard C. Holz.

Additional information

Molecular graphics were created and analyses were performed with the UCSF Chimera package (http://www.cgl.ucsf.edu/chimera). Chimera is developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from the National Institutes of Health (National Center for Research Resources grant 2P41RR001081, National Institute of General Medical Sciences grant 9P41GM103311).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gillner, D.M., Becker, D.P. & Holz, R.C. Lysine biosynthesis in bacteria: a metallodesuccinylase as a potential antimicrobial target. J Biol Inorg Chem 18, 155–163 (2013). https://doi.org/10.1007/s00775-012-0965-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-012-0965-1

Keywords

Search

Navigation