Premium
Head‐to‐Head Prenyl Synthases in Pathogenic Bacteria
Author(s) -
Schwalen Christopher J.,
Feng Xinxin,
Liu Weidong,
ODowd Bing,
Ko TzuPing,
Shin Christopher J.,
Guo ReyTing,
Mitchell Douglas A.,
Oldfield Eric
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700099
Subject(s) - enterococcus hirae , neisseria , biochemistry , biology , staphylococcus aureus , farnesyl pyrophosphate , prenylation , microbiology and biotechnology , bacteria , carica , enzyme , mutagenesis , mutant , biosynthesis , chemistry , genetics , enterococcus , botany , gene
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.