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PDBsum entry 4ph6
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References listed in PDB file
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Key reference
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Title
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Identification of polyketide inhibitors targeting 3-Dehydroquinate dehydratase in the shikimate pathway of enterococcus faecalis.
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Authors
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V.W.Cheung,
B.Xue,
M.Hernandez-Valladares,
M.K.Go,
A.Tung,
A.H.Aguda,
R.C.Robinson,
W.S.Yew.
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Ref.
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Plos One, 2014,
9,
e103598.
[DOI no: ]
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PubMed id
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Abstract
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Due to the emergence of resistance toward current antibiotics, there is a
pressing need to develop the next generation of antibiotics as therapeutics
against infectious and opportunistic diseases of microbial origins. The
shikimate pathway is exclusive to microbes, plants and fungi, and hence is an
attractive and logical target for development of antimicrobial therapeutics. The
Gram-positive commensal microbe, Enterococcus faecalis, is a major human
pathogen associated with nosocomial infections and resistance to vancomycin, the
"drug of last resort". Here, we report the identification of several
polyketide-based inhibitors against the E. faecalis shikimate pathway enzyme,
3-dehydroquinate dehydratase (DHQase). In particular, marein, a flavonoid
polyketide, both inhibited DHQase and retarded the growth of Enterococcus
faecalis. The purification, crystallization and structural resolution of
recombinant DHQase from E. faecalis (at 2.2 Å resolution) are also reported.
This study provides a route in the development of polyketide-based antimicrobial
inhibitors targeting the shikimate pathway of the human pathogen E. faecalis.
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