Protein Posttranslational Modifications: The Chemistry of Proteome Diversifications

Walsh, Christopher T.; Garneau‐Tsodikova, Sylvie; Gatto, Gregory J.

doi:10.1002/anie.200501023

Cited by 1,333 publications

(1,101 citation statements)

References 127 publications

(182 reference statements)

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“…The development of enzyme-modified peptide tags greatly benefit from cell posttranslational modifications (PTMs) carried out by enzymes that form covalent bonds between specific peptide sequences and their corresponding substrate [45]. Selectivity for the modification of a peptide is mediated by an enzyme that recognizes both the specific peptide sequence and the substrate for modification (e.g.…”

Section: Enzyme Mediated Peptide Tagsmentioning

confidence: 99%

Chemical tags: Applications in live cell fluorescence imaging

Wombacher

Cornish

2011

Journal of Biophotonics

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Technologies to visualize cellular structures and dynamics enable cell biologists to gain insight into complex biological processes. Currently, fluorescent proteins are used routinely to investigate the behavior of proteins in live cells. Chemical biology techniques for selective labeling of proteins with fluorescent labels have become an attractive alternative to fluorescent protein labeling. In the last ten years the progress in the development of chemical tagging methods have been substantial offering a broad palette of applications for live cell fluorescent microscopy. Several methods for protein labeling have been established, using protein tags, peptide tags and enzyme mediated tagging. This review focuses on the different strategies to achieve the attachment of fluorophores to proteins in live cells and cast light on the advantages and disadvantages of each individual method. Selected experiments in which chemical tags have been successfully applied to live cell imaging will be discussed and evaluated. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

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Section: Enzyme Mediated Peptide Tagsmentioning

confidence: 99%

Chemical tags: Applications in live cell fluorescence imaging

Wombacher

Cornish

2011

Journal of Biophotonics

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“…Among these, lysine acetylations and methylations are the most abundant and affect the transcriptional status of the genes associated with the corresponding histones. [1][2][3] The role of these modifications is sequence dependent. Typically acetylation is associated with transcriptionally active genes, while methylation induces transcriptional silencing.…”

mentioning

confidence: 99%

Synthesis of ε-N-propionyl-, ε-N-butyryl-, and ε-N-crotonyl-lysine containing histone H3 using the pyrrolysine system

2013

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Recently new lysine modifications were detected in histones and other proteins. Using the pyrrolysine amber suppression system we genetically inserted three of the new amino acids e-N-propionyl-, e-N-butyryl-, and e-N-crotonyl-lysine site specifically into histone H3. The lysine at position 9 (H3 K9), which is known to be highly modified in chromatin, was replaced by these unnatural amino acids.The histone code is based on the post-translational modification of critical amino acid residues in different histones. Among these, lysine acetylations and methylations are the most abundant and affect the transcriptional status of the genes associated with the corresponding histones. [1][2][3] The role of these modifications is sequence dependent. Typically acetylation is associated with transcriptionally active genes, while methylation induces transcriptional silencing. 4,5 Recently Zhao and co-workers discovered a number of new modified amino acids in histones. [6][7][8] Some of these were also detected in proteins other than histones, raising the possibility that they are of more widespread importance. [9][10][11] The new post-translational modifications (PTMs) are acylated derivatives of lysine at the e-amino position. The acylation partners are propionic acid, butyric acid, malonic acid, succinic acid, crotonic acid or fatty acids. A common characteristic of these compounds is that they are key metabolic intermediates that typically exist as CoA activated thioester species in the cell. 12 It is currently not clear how these newly discovered PTMs are biosynthetically established within the histones and we do not fully understand if and how they influence genetic processes.So far no specific deacylases for e-N-propionyl-or e-Nbutyryl-lysine have been identified. However Sirt5, a member of NAD-dependent sirtuins is able to specifically deacylate e-Nmalonyl-and e-N-succinyllysine. 11 Recently it was discovered that HDAC3 exhibits decrotonylase activity in vitro 13 and it was found that lysine crotonylation activates genes even in a globally repressive environment. 7,14 In order to enable investigation of the new lysine derivatives in histones it is essential to generate histones that contain these amino acids site specifically. 15 In this direction semi-synthetic chemical ligation based methods 16,17 were utilized and chemical methods were employed to generate acetyllysine (Kac) and methylated-lysines or derivatives thereof. [18][19][20][21] Chin and co-workers reported the introduction of Kac into H3 K56 22 using the pyrrolysine system. This system was also employed for the synthesis of monomethyl-and dimethyl-lysine containing histones. 23,24 Schultz et al. recently described the synthesis of histone H2B containing e-N-crotonyllysine at position K11 using an evolved pyrrolysyl-tRNA synthetase from Methanosarcina barkeri. 25 Here we show that the pyrrolysine system can be used to insert e-N-propionyl-(Kpr, 1), e-N-butyryl-(Kbu, 2), and e-Ncrotonyl-lysine (Kcr, 3) into histones at critical positions such as H3 K9 using...

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“…The inventory of proteins in a eucaryotic cell is increased significantly by covalent modifications to amino acid sidechains or to the polypeptide backbone [1]. These posttranslational modifications represent the most common mechanism by which the functions of proteins can be altered.…”

Section: Multisite Protein Modificationmentioning

confidence: 99%

“…These phosphorylation events control a multitude of cellular functions [1,[13][14][15]. It is increasingly clear that the activities of many proteins are regulated by phosphorylation at more than one site.…”

Section: Multisite Phosphorylationmentioning

confidence: 99%

Processive phosphorylation: Mechanism and biological importance

Patwardhan

Miller

2007

Cellular Signalling

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Recent proteomic data indicate that a majority of the phosphorylated proteins in a eucaryotic cell contain multiple sites of phosphorylation. In many signaling events, a single kinase phosphorylates multiple sites on a target protein. Processive phosphorylation occurs when a protein kinase binds once to a substrate and phosphorylates all of the available sites before dissociating. In this review, we discuss examples of processive phosphorylation by serine/threonine kinases and tyrosine kinases. We describe current experimental approaches for distinguishing processive from non-processive phosphorylation. Finally, we contrast the biological situations that are suited to regulation by processive and non-processive phosphorylation.

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Protein Posttranslational Modifications: The Chemistry of Proteome Diversifications

Cited by 1,333 publications

References 127 publications

Chemical tags: Applications in live cell fluorescence imaging

Chemical tags: Applications in live cell fluorescence imaging

Synthesis of ε-N-propionyl-, ε-N-butyryl-, and ε-N-crotonyl-lysine containing histone H3 using the pyrrolysine system

Processive phosphorylation: Mechanism and biological importance

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