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B6db references: 29516565

type Journal Article
authors Dow GT, Thoden JB, Holden HM
title The Three-Dimensional Structure of NeoB: An Aminotransferase Involved in the Biosynthesis of Neomycin
journal Protein Sci
sel selected
ui 29516565
year (2018)
volume 27
number 5
pages 945-956
keywords X-ray structure; aminoglycoside antibiotics; aminotransferase; gentamicin; neomycin; pyridoxal 5'-phosphate
abstract The aminoglycoside antibiotics, discovered as natural products in the 1940s, demonstrate a broad anti-microbial 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 anti-parallel 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. This article is protected by copyright. All rights reserved.
last changed 2018/10/05 11:54

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