Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Am Chem Soc
2018 Aug 01;14030:9478-9485. doi: 10.1021/jacs.8b03572.
Show Gene links
Show Anatomy links
Hydrazide Mimics for Protein Lysine Acylation To Assess Nucleosome Dynamics and Deubiquitinase Action.
Bhat S
,
Hwang Y
,
Gibson MD
,
Morgan MT
,
Taverna SD
,
Zhao Y
,
Wolberger C
,
Poirier MG
,
Cole PA
.
???displayArticle.abstract???
A range of acyl-lysine (acyl-Lys) modifications on histones and other proteins have been mapped over the past decade but for most, their functional and structural significance remains poorly characterized. One limitation in the study of acyl-Lys containing proteins is the challenge of producing them or their mimics in site-specifically modified forms. We describe a cysteine alkylation-based method to install hydrazide mimics of acyl-Lys post-translational modifications (PTMs) on proteins. We have applied this method to install mimics of acetyl-Lys, 2-hydroxyisobutyryl-Lys, and ubiquityl-Lys that could be recognized selectively by relevant acyl-Lys modification antibodies. The acyl-Lys modified histone H3 proteins were reconstituted into nucleosomes to study nucleosome dynamics and stability as a function of modification type and site. We also installed a ubiquityl-Lys mimic in histone H2B and generated a diubiquitin analog, both of which could be cleaved by deubiquitinating enzymes. Nucleosomes containing the H2B ubiquityl-Lys mimic were used to study the SAGA deubiquitinating module's molecular recognition. These results suggest that acyl-Lys mimics offer a relatively simple and promising strategy to study the role of acyl-Lys modifications in the function, structure, and regulation of proteins and protein complexes.
???displayArticle.pubmedLink???
29991262
???displayArticle.pmcLink???PMC6070418 ???displayArticle.link???J Am Chem Soc ???displayArticle.grants???[+]
Allfrey,
Structural Modifications of Histones and their Possible Role in the Regulation of RNA Synthesis.
1964, Pubmed
Allfrey,
Structural Modifications of Histones and their Possible Role in the Regulation of RNA Synthesis.
1964,
Pubmed
Bannister,
Regulation of chromatin by histone modifications.
2011,
Pubmed
Bos,
A Chemical Probe for Protein Crotonylation.
2018,
Pubmed
Chalker,
Conversion of cysteine into dehydroalanine enables access to synthetic histones bearing diverse post-translational modifications.
2012,
Pubmed
Chatterjee,
Histone Acetylation near the Nucleosome Dyad Axis Enhances Nucleosome Disassembly by RSC and SWI/SNF.
2015,
Pubmed
,
Xenbase
Chatterjee,
Disulfide-directed histone ubiquitylation reveals plasticity in hDot1L activation.
2010,
Pubmed
Chiang,
A semisynthetic strategy to generate phosphorylated and acetylated histone H2B.
2009,
Pubmed
Cole,
Chemical probes for histone-modifying enzymes.
2008,
Pubmed
Dai,
Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark.
2014,
Pubmed
Dancy,
Azalysine analogues as probes for protein lysine deacetylation and demethylation.
2012,
Pubmed
Davey,
Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution.
2002,
Pubmed
,
Xenbase
Dawson,
Synthesis of proteins by native chemical ligation.
1994,
Pubmed
El Oualid,
Chemical synthesis of ubiquitin, ubiquitin-based probes, and diubiquitin.
2010,
Pubmed
Fierz,
Stability of nucleosomes containing homogenously ubiquitylated H2A and H2B prepared using semisynthesis.
2012,
Pubmed
Gattner,
Synthesis of ε-N-propionyl-, ε-N-butyryl-, and ε-N-crotonyl-lysine containing histone H3 using the pyrrolysine system.
2013,
Pubmed
Henry,
Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8.
2003,
Pubmed
Hirschey,
Metabolic Regulation by Lysine Malonylation, Succinylation, and Glutarylation.
2015,
Pubmed
Huang,
Site-specific introduction of an acetyl-lysine mimic into peptides and proteins by cysteine alkylation.
2010,
Pubmed
Huang,
Quantitative proteomic analysis of histone modifications.
2015,
Pubmed
Huang,
Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation pathway.
2018,
Pubmed
Jing,
Site-Specific Installation of Succinyl Lysine Analog into Histones Reveals the Effect of H2BK34 Succinylation on Nucleosome Dynamics.
2018,
Pubmed
Karukurichi,
Analysis of p300/CBP histone acetyltransferase regulation using circular permutation and semisynthesis.
2010,
Pubmed
Kent,
Total chemical synthesis of proteins.
2009,
Pubmed
Kumar,
Total chemical synthesis of a 304 amino acid K48-linked tetraubiquitin protein.
2011,
Pubmed
Kumar,
Total chemical synthesis of di-ubiquitin chains.
2010,
Pubmed
Köhler,
Structural basis for assembly and activation of the heterotetrameric SAGA histone H2B deubiquitinase module.
2010,
Pubmed
Le,
Site-specific and regiospecific installation of methylarginine analogues into recombinant histones and insights into effector protein binding.
2013,
Pubmed
Li,
A direct method for site-specific protein acetylation.
2011,
Pubmed
Li,
New semi-synthesis of ubiquitin C-terminal conjugate with 7-amino-4-methylcoumarin.
2014,
Pubmed
Li,
The role of chromatin during transcription.
2007,
Pubmed
Lin,
Protein lysine acylation and cysteine succination by intermediates of energy metabolism.
2012,
Pubmed
Manohar,
Acetylation of histone H3 at the nucleosome dyad alters DNA-histone binding.
2009,
Pubmed
,
Xenbase
McGinty,
Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation.
2008,
Pubmed
,
Xenbase
McGinty,
Semisynthesis of ubiquitylated proteins.
2009,
Pubmed
Miller,
A bromodomain-DNA interaction facilitates acetylation-dependent bivalent nucleosome recognition by the BET protein BRDT.
2016,
Pubmed
Morgan,
Structural basis for histone H2B deubiquitination by the SAGA DUB module.
2016,
Pubmed
,
Xenbase
Muir,
Expressed protein ligation: a general method for protein engineering.
1998,
Pubmed
Neumann,
Genetically encoding N(epsilon)-acetyllysine in recombinant proteins.
2008,
Pubmed
Neumann,
A method for genetically installing site-specific acetylation in recombinant histones defines the effects of H3 K56 acetylation.
2009,
Pubmed
Nguyen,
Accelerated chromatin biochemistry using DNA-barcoded nucleosome libraries.
2014,
Pubmed
North,
Regulation of the nucleosome unwrapping rate controls DNA accessibility.
2012,
Pubmed
,
Xenbase
Olsen,
An update on lysine deacylases targeting the expanding "acylome".
2014,
Pubmed
Rousseaux,
Histone Acylation beyond Acetylation: Terra Incognita in Chromatin Biology.
2015,
Pubmed
Rösner,
Click chemistry for targeted protein ubiquitylation and ubiquitin chain formation.
2015,
Pubmed
Samara,
Structural insights into the assembly and function of the SAGA deubiquitinating module.
2010,
Pubmed
Schulze,
Splitting the task: Ubp8 and Ubp10 deubiquitinate different cellular pools of H2BK123.
2011,
Pubmed
Schwarzer,
Protein semisynthesis and expressed protein ligation: chasing a protein's tail.
2005,
Pubmed
Shimko,
Preparation of fully synthetic histone H3 reveals that acetyl-lysine 56 facilitates protein binding within nucleosomes.
2011,
Pubmed
Shogren-Knaak,
Histone H4-K16 acetylation controls chromatin structure and protein interactions.
2006,
Pubmed
Simon,
The site-specific installation of methyl-lysine analogs into recombinant histones.
2007,
Pubmed
,
Xenbase
Simon,
Histone fold modifications control nucleosome unwrapping and disassembly.
2011,
Pubmed
Valkevich,
Forging isopeptide bonds using thiol-ene chemistry: site-specific coupling of ubiquitin molecules for studying the activity of isopeptidases.
2012,
Pubmed
Virdee,
Engineered diubiquitin synthesis reveals Lys29-isopeptide specificity of an OTU deubiquitinase.
2010,
Pubmed
Virdee,
Traceless and site-specific ubiquitination of recombinant proteins.
2011,
Pubmed
Wan,
A facile system for genetic incorporation of two different noncanonical amino acids into one protein in Escherichia coli.
2010,
Pubmed
Wang,
A Versatile Approach for Site-Specific Lysine Acylation in Proteins.
2017,
Pubmed
Wang,
A Chemical Biology Approach to Reveal Sirt6-targeted Histone H3 Sites in Nucleosomes.
2016,
Pubmed
Wang,
Identification and characterization of a novel p300-mediated p53 acetylation site, lysine 305.
2003,
Pubmed
Wang,
Evidence for bidentate substrate binding as the basis for the K48 linkage specificity of otubain 1.
2009,
Pubmed
Wollebo,
The Brd4 acetyllysine-binding protein is involved in activation of polyomavirus JC.
2016,
Pubmed
Yang,
Dual native chemical ligation at lysine.
2009,
Pubmed
Zhang,
An Interaction Landscape of Ubiquitin Signaling.
2017,
Pubmed
Zhao,
Identification of Proteins Interacting with Ubiquitin Chains.
2017,
Pubmed
