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PDBsum entry 6o15
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Oxidoreductase
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PDB id
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6o15
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References listed in PDB file
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Key reference
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Title
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On the structure and function of escherichia coli yjhc: an oxidoreductase involved in bacterial sialic acid metabolism.
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Authors
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C.R.Horne,
L.Kind,
J.S.Davies,
R.C.J.Dobson.
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Ref.
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Proteins, 2020,
88,
654-668.
[DOI no: ]
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PubMed id
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Abstract
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Human pathogenic and commensal bacteria have evolved the ability to scavenge
host-derived sialic acids and subsequently degrade them as a source of
nutrition. Expression of the Escherichia coli yjhBC operon is controlled by the
repressor protein nanR, which regulates the core machinery responsible for the
import and catabolic processing of sialic acid. The role of the yjhBC encoded
proteins is not known-here, we demonstrate that the enzyme YjhC is an
oxidoreductase/dehydrogenase involved in bacterial sialic acid degradation.
First, we demonstrate in vivo using knockout experiments that YjhC is broadly
involved in carbohydrate metabolism, including that of N-acetyl-d-glucosamine,
N-acetyl-d-galactosamine and N-acetylneuraminic acid. Differential scanning
fluorimetry demonstrates that YjhC binds N-acetylneuraminic acid and its lactone
variant, along with NAD(H), which is consistent with its role as an
oxidoreductase. Next, we solved the crystal structure of YjhC in complex with
the NAD(H) cofactor to 1.35 Å resolution. The protein fold belongs to the
Gfo/Idh/MocA protein family. The dimeric assembly observed in the crystal form
is confirmed through solution studies. Ensemble refinement reveals a flexible
loop region that may play a key role during catalysis, providing essential
contacts to stabilize the substrate-a unique feature to YjhC among closely
related structures. Guided by the structure, in silico docking experiments
support the binding of sialic acid and several common derivatives in the binding
pocket, which has an overall positive charge distribution. Taken together, our
results verify the role of YjhC as a bona fide oxidoreductase/dehydrogenase and
provide the first evidence to support its involvement in sialic acid metabolism.
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Secondary reference #1
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Title
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Structural and functional features of the NAD(p) dependent gfo/idh/moca protein family oxidoreductases.
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Authors
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H.Taberman,
T.Parkkinen,
J.Rouvinen.
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Ref.
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Protein Sci, 2016,
25,
778-786.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Unified theory of bacterial sialometabolism: how and bacteria metabolize host sialic acids.
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Author
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E.R.Vimr.
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Ref.
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isrn microbiol, 2013,
2013,
16713.
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PubMed id
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