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PDBsum entry 5nif
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Contents |
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241 a.a.
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250 a.a.
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241 a.a.
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241 a.a.
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236 a.a.
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232 a.a.
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244 a.a.
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196 a.a.
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222 a.a.
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204 a.a.
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196 a.a.
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212 a.a.
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222 a.a.
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232 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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Crystal structure of a low molecular weight activator blm-Pep with yeast 20s proteasome - Insights into the enzyme activation mechanism.
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Authors
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J.Witkowska,
M.Giżyńska,
P.Grudnik,
P.Golik,
P.Karpowicz,
A.Giełdoń,
G.Dubin,
E.Jankowska.
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Ref.
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Sci Rep, 2017,
7,
6177.
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PubMed id
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Abstract
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Proteasomes are responsible for protein turnover in eukaryotic cells, degrading
short-lived species but also removing improperly folded or oxidatively damaged
ones. Dysfunction of a proteasome results in gradual accumulation of
misfolded/damaged proteins, leading to their aggregation. It has been postulated
that proteasome activators may facilitate removal of such aggregation-prone
proteins and thus prevent development of neurodegenerative disorders. However,
the discovery of pharmacologically relevant compounds is hindered by
insufficient structural understanding of the activation process. In this study
we provide a model peptidic activator of human proteasome and analyze the
structure-activity relationship within this novel scaffold. The binding mode of
the activator at the relevant pocket within the proteasome has been determined
by X-ray crystallography. This crystal structure provides an important basis for
rational design of pharmacological compounds. Moreover, by providing a novel
insight into the proteasome gating mechanism, our results allow the commonly
accepted model of proteasome regulation to be revisited.
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