Kumar, Sanjeev ; Prakash, Sunita ; Gupta, Kallol ; Dongre, Aparna ; Balaram, Padmanabhan ; Balaram, Hemalatha (2016) Unexpected functional implication of a stable succinimide in the structural stability of Methanocaldococcus jannaschii glutaminase Nature Communications, 7 (1). ISSN 2041-1723
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Official URL: http://doi.org/10.1038/ncomms12798
Related URL: http://dx.doi.org/10.1038/ncomms12798
Abstract
Protein ageing is often mediated by the formation of succinimide intermediates. These short-lived intermediates derive from asparaginyl deamidation and aspartyl dehydration and are rapidly converted into β-aspartyl or D-aspartyl residues. Here we report the presence of a highly stable succinimide intermediate in the glutaminase subunit of GMP synthetase from the hyperthermophile Methanocaldoccocus jannaschii. By comparing the biophysical properties of the wild-type protein and of several mutants, we show that the presence of succinimide increases the structural stability of the glutaminase subunit. The protein bearing this modification in fact remains folded at 100 °C and in 8 M guanidinium chloride. Mutation of the residue following the reactive asparagine provides insight into the factors that contribute to the hydrolytic stability of the succinimide. Our findings suggest that sequences that stabilize succinimides from hydrolysis may be evolutionarily selected to confer extreme thermal stability.
Item Type: | Article |
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Source: | Copyright of this article belongs to Springer Nature Limited. |
ID Code: | 128715 |
Deposited On: | 02 Nov 2022 11:12 |
Last Modified: | 30 Jan 2023 09:24 |
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