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PDBsum entry 3ccd
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References listed in PDB file
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Key reference
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Title
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Structural investigation of a phosphorylation-Catalyzed, Isoaspartate-Free, Protein succinimide: crystallographic structure of post-Succinimide his15asp histidine-Containing protein.
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Authors
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S.Napper,
L.Prasad,
L.T.Delbaere.
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Ref.
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Biochemistry, 2008,
47,
9486-9496.
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PubMed id
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Abstract
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Aspartates and asparagines can spontaneously cyclize with neighboring main-chain
amides to form succinimides. These succinimides hydrolyze to a mixture of
isoaspartate and aspartate products. Phosphorylation of aspartates is a common
mechanism of protein regulation and increases the propensity for succinimide
formation. Although typically regarded as a form of protein damage, we
hypothesize succinimides could represent an effective mechanism of
phosphoaspartate autophosphatase activity, provided hydrolysis is limited to
aspartate products. We previously reported the serendipitous creation of a
protein, His15Asp histidine-containing protein (HPr), which undergoes
phosphorylation-catalyzed formation of a succinimide whose hydrolysis is
seemingly exclusive for aspartate formation. Here, through the high-resolution
structure of postsuccinimide His15Asp HPr, we confirm the absence of
isoaspartate residues and propose mechanisms for phosphorylation-catalyzed
succinimide formation and its directed hydrolysis to aspartate. His15Asp HPr
represents the first characterized protein example of an isoaspartate-free
succinimide and lends credence to the hypothesis that intramolecular cyclization
could represent a physiological mechanism of autophosphatase activity.
Furthermore, this indicates that current strategies for succinimide evaluation,
based on isoaspartate detection, underestimate the frequencies of these
reactions. This is considerably significant for evaluation of protein stability
and integrity.
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