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PDBsum entry 5mcp
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Oxidoreductase
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PDB id
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5mcp
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Contents |
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440 a.a.
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387 a.a.
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342 a.a.
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382 a.a.
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321 a.a.
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References listed in PDB file
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Key reference
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Title
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A nucleotide-Controlled conformational switch modulates the activity of eukaryotic imp dehydrogenases.
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Authors
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R.M.Buey,
D.Fernández-Justel,
..Marcos-Alcalde,
G.Winter,
P.Gómez-Puertas,
J.M.De pereda,
J.Luis revuelta.
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Ref.
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Sci Rep, 2017,
7,
2648.
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PubMed id
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Abstract
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Inosine-5'-monophosphate dehydrogenase (IMPDH) is an essential enzyme for
nucleotide metabolism and cell proliferation. Despite IMPDH is the target of
drugs with antiviral, immunosuppressive and antitumor activities, its
physiological mechanisms of regulation remain largely unknown. Using the enzyme
from the industrial fungus Ashbya gossypii, we demonstrate that the binding of
adenine and guanine nucleotides to the canonical nucleotide binding sites of the
regulatory Bateman domain induces different enzyme conformations with
significantly distinct catalytic activities. Thereby, the comparison of their
high-resolution structures defines the mechanistic and structural details of a
nucleotide-controlled conformational switch that allosterically modulates the
catalytic activity of eukaryotic IMPDHs. Remarkably, retinopathy-associated
mutations lie within the mechanical hinges of the conformational change,
highlighting its physiological relevance. Our results expand the mechanistic
repertoire of Bateman domains and pave the road to new approaches targeting
IMPDHs.
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