Abstract：
:Functional amino acids that play critical roles in catalysis and regulation are known to display elevated nucleophilicity and can be selectively targeted for covalent modification by reactive electrophiles. Chemical-proteomic platforms, such as activity-based protein profiling (ABPP), exploit this reactivity by utilizing chemical probes to covalently modify active-site residues to inform on the functional state of enzymes within complex proteomes. These and other applications rely on the availability of a diverse array of electrophiles and detailed knowledge of the reactivity and amino-acid selectivity of these groups. Here, we survey the current landscape of electrophiles that covalently target various nucleophilic amino acids in proteins and highlight proteomic applications that have benefited from the unique properties of these electrophiles.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Shannon DA,Weerapana Edoi
10.1016/j.cbpa.2014.10.021subject
Has Abstractpub_date
2015-02-01 00:00:00pages
18-26eissn
1367-5931issn
1879-0402pii
S1367-5931(14)00161-6journal_volume
24pub_type
杂志文章,评审abstract：:Methanogenesis from trimethylamine, dimethylamine or monomethylamine is initiated by a series of corrinoid-dependent methyltransferases. The non-homologous genes encoding the full-length methyltransferases each possess an in-frame UAG (amber) codon that does not terminate translation. The amber codon is decoded by a d...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.08.012
更新日期：2004-10-01 00:00:00
abstract：:Metabolomics and lipidomics aim to comprehensively measure the dynamic changes of all metabolites and lipids that are present in biological systems. The use of ion mobility-mass spectrometry (IM-MS) for metabolomics and lipidomics has facilitated the separation and the identification of metabolites and lipids in compl...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2017.10.033
更新日期：2018-02-01 00:00:00
abstract：:Bacterial-derived antimicrobial polypeptides enjoy a large degree of structural and chemical diversity. Two well-studied examples of such polypeptides are the lanthionine-containing lantibiotics produced by a variety of Gram-positive bacteria, and their Gram-negative counterparts, the microcins. Both groups are produc...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00094-6
更新日期：2000-06-01 00:00:00
abstract：:A variety of protein sequence databases exist, ranging from simple sequence repositories, which store data with little or no manual intervention in the creation of the records, to expertly curated universal databases that cover all species and in which the original sequence data are enhanced by the manual addition of ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2003.12.004
更新日期：2004-02-01 00:00:00
abstract：:The translation of nucleic acids into synthetic structures with expanded functional potential has been the subject of considerable research, with applications including small-molecule and polymer evolution, reaction discovery and sensing. Here, we review properties of nucleic-acid-templated synthesis in the context of...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.09.003
更新日期：2004-12-01 00:00:00
abstract：:Oxidative cysteine modifications have emerged as a central mechanism for dynamic post-translational regulation of all major protein classes and correlate with many disease states. Elucidating the precise roles of cysteine oxidation in physiology and pathology presents a major challenge. This article reviews the curren...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2010.11.012
更新日期：2011-02-01 00:00:00
abstract：:Small molecule production in microbial hosts is limited by the accumulation of the product inside the cell. Efflux transporters show promise as a solution to removal of the often-toxic products. Recent advances in transporter identification through expression profiling, heterologous expression, and knockout studies ha...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2015.05.019
更新日期：2015-10-01 00:00:00
abstract：:Natural enzymes that catalyze Diels-Alder reactions have long been sought after, yet few enzymes have been experimentally confirmed to perform this reaction. In the past five years, several stand-alone enzymes that can catalyze the Diels-Alder reaction had been identified and characterized. Among which, the crystal st...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.09.015
更新日期：2016-12-01 00:00:00
abstract：:The principles of enzyme chemistry, mechanism of action and inhibitor design are being applied to proteomics by the development of activity-based probes. This approach suggests a potentially broad method for interrogating enzyme family members, both known and unknown, in cells and proteomic fractions without the need ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00013-3
更新日期：2003-02-01 00:00:00
abstract：:RNA plays an essential cellular role in nearly every aspect of the transmission and expression of genetic information, including regulatory roles that have significance for cellular development. Access to RNA bearing synthetic modifications has allowed biological chemists to probe deep into the inner workings of cellu...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2005.10.009
更新日期：2005-12-01 00:00:00
abstract：:A wide assortment of caged compounds, which are species whose biological activity can be unleashed with light, have been synthesized and used to investigate a variety of biological phenomena. In contrast, the construction of caged proteins and their application to biological systems has lagged far behind. Recent advan...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(99)80015-5
更新日期：1999-02-01 00:00:00
abstract：:Cellular communication drives diverse aspects of organismal biology ranging from immune function to memory formation. The mechanisms by which cells transact information in vivo, though, are not completely understood. This is due, in part, to a lack of tools for observing collections of cells in their native habitats. ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2014.11.006
更新日期：2015-02-01 00:00:00
abstract：:New insights have been gained into the formation of the di-iron tyrosyl radical cofactor, which is essential for nucleotide reduction in the class I ribonucleotide reductases. Recent advances include Insight into the function of the tyrosyl radical in initiation of nucleotide reduction. ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(03)00025-5
更新日期：2003-04-01 00:00:00
abstract：:Compartmentalization is one of the defining features of life. Cells use protein compartments to exert spatial control over their metabolism, store nutrients and create unique microenvironments needed for essential physiological processes. Encapsulins are a recently discovered class of protein nanocompartments found in...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.05.013
更新日期：2016-10-01 00:00:00
abstract：:Oligosaccharyl transferase is part of the macromolecular machinery that processes nascent proteins in the endoplasmic reticulum. The enzyme is highly conserved, catalyzes the initial step in the biosynthesis of N-linked glycoproteins and acts as a 'gatekeeper' for the secretory pathway. As more proteins associated wit...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00390-3
更新日期：2002-12-01 00:00:00
abstract：:Nanoparticle-based therapeutics have received increasing attention, as these systems can alleviate many drawbacks of conventional therapy. Metal-organic frameworks (MOFs), a new class of hybrid materials composed of metal ions and organic bridging ligands, have emerged as a promising platform for drug delivery, owing ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2009.12.012
更新日期：2010-04-01 00:00:00
abstract：:Fourier transform infrared (FTIR) spectroscopy has long been a powerful tool for structural analysis of membrane proteins. However, because of difficulties in resolving contributions from individual residues, most of the derived measurements tend to yield average properties for the system under study. Isotope editing,...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2006.08.013
更新日期：2006-10-01 00:00:00
abstract：:There is growing interest in the design of synthetic molecules that mimic the structures and functions of epitopes found on the surface of peptides and proteins. Epitope mimetics can provide valuable tools to probe complex biological processes, as well as interesting leads for drug and vaccine discovery. One applicati...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2011.02.015
更新日期：2011-06-01 00:00:00
abstract：:The manufacture and use of protein microarrays with correctly folded and functional content presents significant challenges. Despite this, the feasibility and utility of such undertakings are now clear, and exciting progress has recently been demonstrated in the areas of content generation, printing strategies and pro...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2003.12.005
更新日期：2004-02-01 00:00:00
abstract：:Nitrogenase catalyzes the important reactions of N2-reduction, CO-reduction and CO2-reduction at its active cofactor site. Designated the M-cluster, this complex metallocofactor is assembled through the generation of a characteristic 8Fe-core before the insertion of Mo and homocitrate that completes the stoichiometry ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2016.02.016
更新日期：2016-04-01 00:00:00
abstract：:The catalytic pathways of soluble methane monooxygenase (sMMO) and cytochrome P450CAM, iron-containing enzymes, are described and compared. Recent extensive density functional ab initio electronic structure calculations have revealed many similarities in a number of the key catalytic steps, as well as some important d...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00310-1
更新日期：2002-04-01 00:00:00
abstract：:Natural products continue to provide privileged scaffolds for drug discovery. However, challenges in supply and structure diversification can limit development. Here, we discuss recent (2017-2020) examples of synthetic biology approaches used to address challenges in supply and contribute to structure diversification ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2020.09.006
更新日期：2020-10-01 00:00:00
abstract：:Significant progress in our understanding of the mechanism of fatty acid desaturation has been achieved. The site of initial oxidation has been determined for several membrane-bound desaturases and a common cryptoregiochemical theme has been revealed. The results of several studies, including a detailed analysis of a ...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(02)00365-4
更新日期：2002-10-01 00:00:00
abstract：:Aside from the demonstration that individual molecular traits of enzymes can be evolutionarily optimised, the discovery that several traits can be simultaneously optimised is a major advance. The first observations of the effects of evolutionary optimisation at the structural level, through X-ray crystallography, rein...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00087-9
更新日期：2000-06-01 00:00:00
abstract：:Numerous developments in useful linkers are closely related with the advances in solid-phase organic synthesis. These linkers allow facile attachment functionalization and release molecules of interest. Designing a new anchoring group can be essential for synthesis success, especially for small molecules on solid supp...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.04.004
更新日期：2004-06-01 00:00:00
abstract：:Chromatin organization spans a wide range of structural complexity. Substructures at the 10-200nm scale are poorly characterized, especially in living cells, due to the limitations of electron microscopy and standard optical microscopy. Recently developed super-resolution fluorescence microscopy methods represent an e...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2011.10.004
更新日期：2011-12-01 00:00:00
abstract：:In many species, double-stranded RNA can specifically and effectively silence genes. This newly discovered biological phenomenon, called RNA interference (RNAi), has practical implications for functional genomics. As shown by two recent reports, RNAi provides a rapid method to test the function of genes in the nematod...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(00)00173-3
更新日期：2001-02-01 00:00:00
abstract：:RNA editing in kinetoplastids involves post-transcriptional insertion and deletion of uridylates (Us) to produce mature mitochondrial mRNAs with sequences specified by trans acting small guide RNAs. In vitro studies indicate the reaction pathway involves endonucleolytic cleavage of the precursor mRNA at the editing si...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/s1367-5931(97)80071-3
更新日期：1997-10-01 00:00:00
abstract：:Natural products containing a gamma-butyrolactone ring are abundant in nature; however, few general synthetic approaches to their stereoselective synthesis with broad structural variety are known. In this article, recent developments towards mono- and polycyclic gamma-butyrolactone natural products and analogs are dis...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2005.03.005
更新日期：2005-06-01 00:00:00
abstract：:Rapid progress in genomics and proteomics has provided a wealth of new targets for the pharmaceutical industry, even as many older targets still remain challenging for small-molecule drug discovery. Fragment-based lead discovery, in which leads are built progressively by expanding or combining small fragments, is a ra...
journal_title：Current opinion in chemical biology
pub_type： 杂志文章,评审
doi：10.1016/j.cbpa.2004.06.010
更新日期：2004-08-01 00:00:00
