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PDBsum entry 2cfc
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Oxidoreductase
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PDB id
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2cfc
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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 basis for stereoselectivity in the (r)- And (s)-Hydroxypropylthioethanesulfonate dehydrogenases.
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Authors
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A.M.Krishnakumar,
B.P.Nocek,
D.D.Clark,
S.A.Ensign,
J.W.Peters.
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Ref.
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Biochemistry, 2006,
45,
8831-8840.
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PubMed id
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Abstract
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Epoxide metabolism in Xanthobacter autotrophicus Py2 results in the conversion
of epoxypropane to acetoacetate. Epoxide metabolism is initiated by the
nucleophilic addition of coenzyme M to the (R)- and (S)-enantiomers of
epoxypropane which forms the respective enantiomers of 2-hydroxypropyl-coenyme
M. The (R)- and (S)-enantiomers of 2-hydroxypropyl coenzyme are oxidized to the
achiral product 2-ketopropyl-CoM by two stereoselective dehydrogenases. The
dehydrogenases catalyzing these reactions, termed (R)-hydroxypropyl-coenzyme M
dehydrogenase (R-HPCDH) and (S)-hydroxypropyl-coenzyme M dehydrogenase
(S-HPCDH), are NAD(+)-dependent enzymes belonging to the short chain
dehydrogenase/reductase (SDR) family of enzymes. In this study, the crystal
structure of R-HPCDH cocrystallized in the presence of
(S)-hydroxypropyl-coenzyme M has been determined using X-ray diffraction methods
and refined to 1.8 A resolution. The structure of R-HPCDH is tetrameric and
stabilized by the interaction of the terminal carboxylates of each subunit with
divalent metal ions. The structure of the presumed product-bound state reveals
that binding interactions between the negatively charged oxygen atoms of the
sulfonate moiety have striking similarities to sulfonate interactions observed
in the previously determined structure of 2-ketopropyl-CoM
oxidoreductase/carboxylase, highlighting the utility of coenzyme M as a carrier
molecule in the pathway. The key elements of the aforementioned interactions are
electrostatic interactions between the sulfonate oxygen atoms and two arginine
residues (R152 and R196) of R-HPCDH. The comparison of the structure of R-HPCDH
with a homology model of S-HPCDH provides a structural basis for a mechanism of
substrate specificity in which the binding of the substrate sulfonate moiety at
distinct sites on each stereoselective enzyme directs the orientation of the
appropriate substrate enantiomer for hydride abstraction.
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