• Corpus ID: 46530211

Pyroglutamic acid : throwing light on a lightly studied metabolite

@inproceedings{Kumar2012PyroglutamicA,
  title={Pyroglutamic acid : throwing light on a lightly studied metabolite},
  author={Akhilesh Kumar and Anand Kumar Bachhawat},
  year={2012}
}
Pyroglutamic acid or 5-oxoproline is the cyclic lactam of glutamic acid. Its presence in living cells has been reported from archaebacteria to humans, and its occurrence in living cells has been known for over a century. Despite its almost ubiquitous presence, the role of pyroglutamic acid in living cells is poorly understood. Pyroglutamic acid is found as an N-terminal modification in many neuronal peptides and hormones that also include the accumulating peptides in Alzheimer’s disease and… 

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References

SHOWING 1-10 OF 92 REFERENCES
Formation of pyroglutamic acid from N-terminal glutamic acid in immunoglobulin gamma antibodies.
TLDR
To the knowledge, it is shown for the first time that glutamic acid residues located at the N-terminus of proteins undergo pyroglutamic acid formation in vitro.
Studies on the accumulation of L-pyroglutamic acid in guinea pig epidermis.
  • S. Marstein
  • Biology, Chemistry
    The Journal of investigative dermatology
  • 1980
TLDR
It is suggested that the only major pathway by which pyroglutamate may be formed in epidermal tissue is from L-glutamate by a 2-step reaction, the first involving the formation of a gamma- glutamyl peptide by the action of gamma-glUTamyl-cysteine synthetase.
N-terminal Glutamate to Pyroglutamate Conversion in Vivo for Human IgG2 Antibodies
TLDR
Investigation of to what extent human IgG2 N-terminal glutamate converts to pE in vivo found differences in the conversion rates between the light chain and heavy chain on an antibody were eliminated by denaturing the protein, revealing that structural elements affect pE formation rates.
Impaired activity of the gamma-glutamyl cycle in nephropathic cystinosis fibroblasts.
TLDR
The hypothesis that cysteine derived from lysosomal cystine efflux limits the activity of the gamma-glutamyl cycle and GSH synthesis is supported.
5-Oxo-~-prolinase (L-Pyroglutamate Hydrolase)
TLDR
It was shown that the enzyme also catalyzes the intrinsically exergonic hydrolysis of cr-hydroxyglutar- ate lactone, a reaction that is ATP-dependent, and the findings are consistent with a mechanism in which B-oxo-~-proline is phosphorylated by ATP on the amide carbonyl oxygen and the resulting intermediate is subsequently hydrolyzed to yield y-glutamyl phos- phate.
The identification and structural characterization of C7orf24 as gamma-glutamyl cyclotransferase. An essential enzyme in the gamma-glutamyl cycle.
TLDR
A potential active site pocket that contains a highly conserved glutamic acid (Glu(98) to Ala or Gln completely inactivates the enzyme without altering the overall fold, and is proposed to refer to this structure as the gamma-glutamyl cyclotransferase fold.
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