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Science
2016 Nov 04;3546312:623-626. doi: 10.1126/science.aah4428.
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A chemical biology route to site-specific authentic protein modifications.
Yang A
,
Ha S
,
Ahn J
,
Kim R
,
Kim S
,
Lee Y
,
Kim J
,
Söll D
,
Lee HY
,
Park HS
.
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Many essential biological processes are controlled by posttranslational protein modifications. The inability to synthetically attain the diversity enabled by these modifications limits functional studies of many proteins. We designed a three-step approach for installing authentic posttranslational modifications in recombinant proteins. We first use the established O-phosphoserine (Sep) orthogonal translation system to create a Sep-containing recombinant protein. The Sep residue is then dephosphorylated to dehydroalanine (Dha). Last, conjugate addition of alkyl iodides to Dha, promoted by zinc and copper, enables chemoselective carbon-carbon bond formation. To validate our approach, we produced histone H3, ubiquitin, and green fluorescent protein variants with site-specific modifications, including different methylations of H3K79. The methylated histones stimulate transcription through histone acetylation. This approach offers a powerful tool to engineer diverse designer proteins.
Chalker,
Conversion of cysteine into dehydroalanine enables access to synthetic histones bearing diverse post-translational modifications.
2012, Pubmed
Chalker,
Conversion of cysteine into dehydroalanine enables access to synthetic histones bearing diverse post-translational modifications.
2012,
Pubmed
Greer,
Histone methylation: a dynamic mark in health, disease and inheritance.
2012,
Pubmed
Guo,
Site-specific incorporation of methyl- and acetyl-lysine analogues into recombinant proteins.
2008,
Pubmed
,
Xenbase
Hart,
Free-radical carbon-carbon bond formation in organic synthesis.
1984,
Pubmed
Hofmann,
A radical approach to posttranslational mutagenesis.
2017,
Pubmed
Kim,
The human PAF1 complex acts in chromatin transcription elongation both independently and cooperatively with SII/TFIIS.
2010,
Pubmed
Lang,
Cellular incorporation of unnatural amino acids and bioorthogonal labeling of proteins.
2014,
Pubmed
Lee,
A facile strategy for selective incorporation of phosphoserine into histones.
2013,
Pubmed
Lipshutz,
C-C bond formation via copper-catalyzed conjugate addition reactions to enones in water at room temperature.
2012,
Pubmed
Liu,
Adding new chemistries to the genetic code.
2010,
Pubmed
Liu,
Synthesis of proteins with defined posttranslational modifications using the genetic noncanonical amino acid incorporation approach.
2011,
Pubmed
Müller,
Histones: at the crossroads of peptide and protein chemistry.
2015,
Pubmed
Nguyen,
Genetically directing ɛ-N, N-dimethyl-L-lysine in recombinant histones.
2010,
Pubmed
Nguyen,
The diverse functions of Dot1 and H3K79 methylation.
2011,
Pubmed
Oda,
Enrichment analysis of phosphorylated proteins as a tool for probing the phosphoproteome.
2001,
Pubmed
Park,
Expanding the genetic code of Escherichia coli with phosphoserine.
2011,
Pubmed
Simon,
The site-specific installation of methyl-lysine analogs into recombinant histones.
2007,
Pubmed
,
Xenbase
Spicer,
Selective chemical protein modification.
2014,
Pubmed
Vinogradova,
Organometallic palladium reagents for cysteine bioconjugation.
2015,
Pubmed
Walsh,
Protein posttranslational modifications: the chemistry of proteome diversifications.
2005,
Pubmed
Wang,
A biosynthetic route to dehydroalanine-containing proteins.
2007,
Pubmed
Zhu,
Convergent synthesis of peptide conjugates using dehydroalanines for chemoselective ligations.
2001,
Pubmed
van Kasteren,
Expanding the diversity of chemical protein modification allows post-translational mimicry.
2007,
Pubmed
