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General assay for enzymes in the heptose biosynthesis pathways using electrospray ionization mass spectrometry

Title
General assay for enzymes in the heptose biosynthesis pathways using electrospray ionization mass spectrometry
Authors
Park J.Lee D.Seo E.K.Ryu J.-S.Shin D.H.
Ewha Authors
서은경류재상신동해
SCOPUS Author ID
서은경scopus; 류재상scopus; 신동해scopus
Issue Date
2017
Journal Title
Applied Microbiology and Biotechnology
ISSN
0175-7598JCR Link
Citation
vol. 101, no. 11, pp. 4521 - 4532
Keywords
Burkholderia pseudomalleiElectrospray ionization mass spectroscopyHeptose biosynthesis pathwaysMelioidosisNucleotide-activated heptose
Publisher
Springer Verlag
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The ADP-l-glycero-β-d-manno-heptose and the GDP-6-deoxy-α-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-α-d-manno-heptose-1-phosphate guanylyltransferase (HddC) included in the GDP-6-deoxy-α-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 α-d-glucose-1-phosphate. (−)-Nyasol exhibits the half maximal inhibitory concentration (IC50) value of 17.6 μM. A further study is going on using (−)-nyasol derivatives to find better leads with high affinity. © 2017, Springer-Verlag Berlin Heidelberg.
DOI
10.1007/s00253-017-8148-1
Appears in Collections:
약학대학 > 약학과 > Journal papers
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