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PDBsum entry 5dz2
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References listed in PDB file
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Key reference
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Title
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Structural studies of geosmin synthase, A bifunctional sesquiterpene synthase with αα domain architecture that catalyzes a unique cyclization-Fragmentation reaction sequence.
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Authors
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G.G.Harris,
P.M.Lombardi,
T.A.Pemberton,
T.Matsui,
T.M.Weiss,
K.E.Cole,
M.Köksal,
F.V.Murphy,
L.S.Vedula,
W.K.Chou,
D.E.Cane,
D.W.Christianson.
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Ref.
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Biochemistry, 2015,
54,
7142-7155.
[DOI no: ]
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PubMed id
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Abstract
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Geosmin synthase from Streptomyces coelicolor (ScGS) catalyzes an unusual,
metal-dependent terpenoid cyclization and fragmentation reaction sequence. Two
distinct active sites are required for catalysis: the N-terminal domain
catalyzes the ionization and cyclization of farnesyl diphosphate to form
germacradienol and inorganic pyrophosphate (PPi), and the C-terminal domain
catalyzes the protonation, cyclization, and fragmentation of germacradienol to
form geosmin and acetone through a retro-Prins reaction. A unique αα domain
architecture is predicted for ScGS based on amino acid sequence: each domain
contains the metal-binding motifs typical of a class I terpenoid cyclase, and
each domain requires Mg(2+) for catalysis. Here, we report the X-ray crystal
structure of the unliganded N-terminal domain of ScGS and the structure of its
complex with three Mg(2+) ions and alendronate. These structures highlight
conformational changes required for active site closure and catalysis. Although
neither full-length ScGS nor constructs of the C-terminal domain could be
crystallized, homology models of the C-terminal domain were constructed on the
basis of ∼36% sequence identity with the N-terminal domain. Small-angle X-ray
scattering experiments yield low-resolution molecular envelopes into which the
N-terminal domain crystal structure and the C-terminal domain homology model
were fit, suggesting possible αα domain architectures as frameworks for
bifunctional catalysis.
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