General assay for enzymes in the heptose biosynthesis pathways using electrospray ionization mass spectrometry
- 주제(키워드) Heptose biosynthesis pathways , Nucleotide-activated heptose , Burkholderia pseudomallei , Melioidosis , Electrospray ionization mass spectroscopy
- 등재 SCIE, SCOPUS
- 발행기관 SPRINGER
- 발행년도 2017
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000144806
- 본문언어 영어
- Published As http://dx.doi.org/10.1007/s00253-017-8148-1
초록/요약
The ADP-l-glycero-beta-d-manno-heptose and the GDP-6-deoxy-alpha-d-manno-heptose biosynthesis pathways play important roles in constructing lipopolysaccharide of Gram-negative bacteria. Blocking the pathways is lethal or increases antibiotic susceptibility to pathogens. Therefore, the enzymes involved in the pathways are novel antibiotic drug targets. Here, we designed an efficient method to assay the whole enzymes in the pathways using mass spectrometry and screened 148 compounds. One promising lead is (-)-nyasol targeting d-glycero-alpha-d-manno-heptose-1-phosphate guanylyltransferase (HddC) included in the GDP-6-deoxy-alpha-d-manno-heptose biosynthesis pathway from Burkholderia pseudomallei. The inhibitory activity of the lead compound against HddC has been confirmed by blocking the system transferring the guanosine monophosphate (GMP) moiety to alpha-d-glucose-1-phosphate. (-)-Nyasol exhibits the half maximal inhibitory concentration (IC50) value of 17.6 mu M. A further study is going on using (-)-nyasol derivatives to find better leads with high affinity.
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