| Autor: |
Fowler, Nicholas, Blanford, Christopher F., De Visser, Samuel, Warwicker, James |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Fowler, N, Blanford, C F, De Visser, S & Warwicker, J 2017, ' Features of reactive cysteines discovered through computation : from kinase inhibition to enrichment around protein degrons. ', Scientific Reports, vol. 7, 16338 . https://doi.org/10.1038/s41598-017-15997-z |
| DOI: |
10.1038/s41598-017-15997-z |
| Popis: |
Large-scale characterisation of cysteine modification is enabling study of the physicochemical determinants of reactivity. We find that location of cysteine at the amino terminus of an α-helix, associated with activity in thioredoxins, is under-represented in human protein structures, perhaps indicative of selection against background reactivity. An amino-terminal helix location underpins thecovalent linkage for one class of kinase inhibitors. Cysteine targets for S-palmitoylation, Sglutathionylation, and S-nitrosylation show little correlation with pKa values predicted from structures, although flanking sequences of S-palmitoylated sites are enriched in positively-charged amino acids, which could facilitate palmitoyl group transfer to substrate cysteine. A surprisinglylarge fraction of modified sites, across the three modifications, would be buried in native protein structure. Furthermore, modified cysteines are (on average) closer to lysine ubiquitinations than are unmodified cysteines, indicating that cysteine redox biology could be associated with protein degradation and degron recognition. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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