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PDBsum entry 4onc
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References listed in PDB file
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Key reference
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Title
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Structure and inhibition of tuberculosinol synthase and decaprenyl diphosphate synthase from mycobacterium tuberculosis.
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Authors
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H.C.Chan,
X.Feng,
T.P.Ko,
C.H.Huang,
Y.Hu,
Y.Zheng,
S.Bogue,
C.Nakano,
T.Hoshino,
L.Zhang,
P.Lv,
W.Liu,
D.C.Crick,
P.H.Liang,
A.H.Wang,
E.Oldfield,
R.T.Guo.
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Ref.
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J Am Chem Soc, 2014,
136,
2892-2896.
[DOI no: ]
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PubMed id
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Abstract
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We have obtained the structure of the bacterial diterpene synthase,
tuberculosinol/iso-tuberculosinol synthase (Rv3378c) from Mycobacterium
tuberculosis , a target for anti-infective therapies that block virulence factor
formation. This phosphatase adopts the same fold as found in the Z- or
cis-prenyltransferases. We also obtained structures containing the
tuberculosinyl diphosphate substrate together with one bisphosphonate
inhibitor-bound structure. These structures together with the results of
site-directed mutagenesis suggest an unusual mechanism of action involving two
Tyr residues. Given the similarity in local and global structure between Rv3378c
and the M. tuberculosis cis-decaprenyl diphosphate synthase (DPPS; Rv2361c), the
possibility exists for the development of inhibitors that target not only
virulence but also cell wall biosynthesis, based in part on the structures
reported here.
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