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PDBsum entry 6cbk
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References listed in PDB file
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Key reference
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Title
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The three-Dimensional structure of neob: an aminotransferase involved in the biosynthesis of neomycin.
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Authors
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G.T.Dow,
J.B.Thoden,
H.M.Holden.
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Ref.
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Protein Sci, 2018,
27,
945-956.
[DOI no: ]
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PubMed id
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Abstract
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The aminoglycoside antibiotics, discovered as natural products in the 1940s,
demonstrate a broad antimicrobial spectrum. Due to their nephrotoxic and
ototoxic side effects, however, their widespread clinical usage has typically
been limited to the treatment of serious infections. Neomycin B, first isolated
from strains of Streptomyces in 1948, is one such drug that was approved for
human use by the U.S. Food and Drug Administration in 1964. Only within the last
11 years has the biochemical pathway for its production been elaborated,
however. Here we present the three-dimensional architecture of NeoB from
Streptomyces fradiae, which is a pyridoxal 5'-phosphate or PLP-dependent
aminotransferase that functions on two different substrates in neomycin B
biosynthesis. For this investigation, four high resolution X-ray structures of
NeoB were determined in various complexed states. The overall fold of NeoB is
that typically observed for members of the "aspartate
aminotransferase" family with the exception of an additional three-stranded
antiparallel β-sheet that forms part of the subunit-subunit interface of the
dimer. The manner in which the active site of NeoB accommodates quite different
substrates has been defined by this investigation. In addition, during the
course of this study, we also determined the structure of the aminotransferase
GenB1 to high resolution. GenB1 functions as an aminotransferase in gentamicin
biosynthesis. Taken together, the structures of NeoB and GenB1, presented here,
provide the first detailed descriptions of aminotransferases that specifically
function on aldehyde moieties in aminoglycoside biosynthesis.
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