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PDBsum entry 5nqb
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Oxidoreductase
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PDB id
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5nqb
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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 self-Inhibitory nature of metabolic networks and its alleviation through compartmentalization.
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Authors
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M.T.Alam,
V.Olin-Sandoval,
A.Stincone,
M.A.Keller,
A.Zelezniak,
B.F.Luisi,
M.Ralser.
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Ref.
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Nat Commun, 2017,
8,
16018.
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Metabolites can inhibit the enzymes that generate them. To explore the general
nature of metabolic self-inhibition, we surveyed enzymological data accrued from
a century of experimentation and generated a genome-scale enzyme-inhibition
network. Enzyme inhibition is often driven by essential metabolites, affects the
majority of biochemical processes, and is executed by a structured network whose
topological organization is reflecting chemical similarities that exist between
metabolites. Most inhibitory interactions are competitive, emerge in the close
neighbourhood of the inhibited enzymes, and result from structural similarities
between substrate and inhibitors. Structural constraints also explain one-third
of allosteric inhibitors, a finding rationalized by crystallographic analysis of
allosterically inhibited L-lactate dehydrogenase. Our findings suggest that the
primary cause of metabolic enzyme inhibition is not the evolution of regulatory
metabolite-enzyme interactions, but a finite structural diversity prevalent
within the metabolome. In eukaryotes, compartmentalization minimizes inevitable
enzyme inhibition and alleviates constraints that self-inhibition places on
metabolism.
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