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PDBsum entry 1udc
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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 analysis of udp-Sugar binding to udp-Galactose 4-Epimerase from escherichia coli.
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Authors
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J.B.Thoden,
A.D.Hegeman,
G.Wesenberg,
M.C.Chapeau,
P.A.Frey,
H.M.Holden.
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Ref.
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Biochemistry, 1997,
36,
6294-6304.
[DOI no: ]
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PubMed id
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Abstract
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UDP-galactose 4-epimerase from Escherichia coli catalyzes the interconversion of
UDP-galactose and UDP-glucose through the transient reduction of the tightly
bound cofactor NAD+. The enzyme is unique among the NAD+-dependent enzymes in
that it promotes stereospecific reduction of the cofactor but nonstereospecific
hydride return during normal catalysis. In addition to hydride transfer, the
reaction mechanism of epimerase involves two key features: the abstraction of a
proton from the 4'-hydroxyl group of glucose or galactose by an active site base
and the rotation of a 4-ketopyranose intermediate in the active site pocket. To
address the second issue of movement within the active site, the X-ray
structures of reduced epimerase complexed with UDP-mannose,
UDP-4-deoxy-4-fluoro-alpha-D-galactose, or UDP-4-deoxy-4-fluoro-alpha-D-glucose
have been determined and refined to 1.65, 1.8, and 1.65 A resolution,
respectively. A comparison of these models to that of the previously determined
epimerase/NADH/UDP-glucose abortive complex reveals that the active site
accommodates the various sugars by simple rearrangements of water molecules
rather than by large changes in side chain conformations. In fact, the
polypeptide chains for all of the epimerase/NADH/UDP-sugar complexes studied
thus far are remarkably similar and can be superimposed with root-mean-square
deviations of not greater than 0.24 A. The only significant differences between
the various enzyme/UDP-sugar models occur in two of the dihedral angles defining
the conformation of the UDP-sugar ligands.
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