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Chembiochem. 2017 Jun 1;18(11):985-991. doi: 10.1002/cbic.201700099. Epub 2017 Apr 25.

Head-to-Head Prenyl Synthases in Pathogenic Bacteria.

Author information

1
Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL, 61801, USA.
2
Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 West 7th Avenue, Tianjin, 300308, China.
3
Institute of Biological Chemistry, Academia Sinica, 128 Academia Road Section 2, Taipei, 11529, Taiwan.
4
Department of Microbiology, University of Illinois, 601 South Goodwin Avenue, Urbana, IL, 61801, USA.
5
Carl R. Woese Institute for Genomic Biology, University of Illinois, 1206 West Gregory Drive, Urbana, IL, 61801, USA.

Abstract

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.

KEYWORDS:

enzyme; isoprenoid synthases; meningitis; squalene; terpenes

PMID:
28340291
PMCID:
PMC5569891
DOI:
10.1002/cbic.201700099
[Indexed for MEDLINE]
Free PMC Article

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