Head-to-Head Prenyl Synthases in Pathogenic Bacteria

Christopher J. Schwalen, Xinxin Feng, Weidong Liu, Bing O-Dowd, Tzu Ping Ko, Christopher J. Shin, Rey Ting Guo, Douglas A. Mitchell, Eric Oldfield

Research output: Contribution to journalArticlepeer-review


Many organisms contain head-to-head isoprenoid synthases; we investigated three such types of enzymes from the pathogens Neisseria meningitidis, Neisseria gonorrhoeae, and Enterococcus hirae. The E. hirae enzyme was found to produce dehydrosqualene, and we solved an inhibitor-bound structure that revealed a fold similar to that of CrtM from Staphylococcus aureus. In contrast, the homologous proteins from Neisseria spp. carried out only the first half of the reaction, yielding presqualene diphosphate (PSPP). Based on product analyses, bioinformatics, and mutagenesis, we concluded that the Neisseria proteins were HpnDs (PSPP synthases). The differences in chemical reactivity to CrtM were due, at least in part, to the presence of a PSPP-stabilizing arginine in the HpnDs, decreasing the rate of dehydrosqualene biosynthesis. These results show that not only S. aureus but also other bacterial pathogens contain head-to-head prenyl synthases, although their biological functions remain to be elucidated.

Original languageEnglish (US)
Pages (from-to)985-991
Number of pages7
Issue number11
StatePublished - Jun 1 2017


  • enzyme
  • isoprenoid synthases
  • meningitis
  • squalene
  • terpenes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry


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