Abstract:
:The chemical species involved in H2S signaling remain elusive despite the profound and pleiotropic physiological effects elicited by this molecule. The dominant candidate mechanism for sulfide signaling is persulfidation of target proteins. However, the relatively poor reactivity of H2S toward oxidized thiols, such as disulfides, the low concentration of disulfides in the reducing milieu of the cell and the low steady-state concentration of H2S raise questions about the plausibility of persulfide formation via reaction between an oxidized thiol and a sulfide anion or a reduced thiol and oxidized hydrogen disulfide. In contrast, sulfide oxidation pathways, considered to be primarily mechanisms for disposing of excess sulfide, generate a series of reactive sulfur species, including persulfides, polysulfides and thiosulfate, that could modify target proteins. We posit that sulfide oxidation pathways mediate sulfide signaling and that sulfurtransferases ensure target specificity.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Mishanina TV,Libiad M,Banerjee Rdoi
10.1038/nchembio.1834subject
Has Abstractpub_date
2015-07-01 00:00:00pages
457-64issue
7eissn
1552-4450issn
1552-4469pii
nchembio.1834journal_volume
11pub_type
杂志文章abstract::Drug discovery resources in academia and industry are not used efficiently, to the detriment of industry and society. Duplication could be reduced, and productivity could be increased, by performing basic biology and clinical proofs of concept within open access industry-academia partnerships. Chemical biologists coul...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio0709-436
更新日期:2009-07-01 00:00:00
abstract::ADP-ribosylation (ADPr) is a biologically and clinically important post-translational modification, but little is known about the amino acids it targets on cellular proteins. Here we present a proteomic approach for direct in vivo identification and quantification of ADPr sites on histones. We have identified 12 uniqu...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2180
更新日期:2016-12-01 00:00:00
abstract::Protein serine-threonine kinase casein kinase II (CK2) is involved in a myriad of cellular processes including cell growth and proliferation through its phosphorylation of hundreds of substrates, yet how CK2 function is regulated is poorly understood. Here we report that the CK2 catalytic subunit CK2α is modified by O...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.771
更新日期:2012-01-22 00:00:00
abstract::5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1848
更新日期:2015-08-01 00:00:00
abstract::Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. We characterized NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader consisting ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2538
更新日期:2018-02-01 00:00:00
abstract::N(1)-Methyladenosine (m(1)A) is a prevalent post-transcriptional RNA modification, yet little is known about its abundance, topology and dynamics in mRNA. Here, we show that m(1)A is prevalent in Homo sapiens mRNA, which shows an m(1)A/A ratio of ∼0.02%. We develop the m(1)A-ID-seq technique, based on m(1)A immunoprec...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2040
更新日期:2016-05-01 00:00:00
abstract::Lipid rafts in plasma membranes have emerged as possible platforms for the entry of HIV and other viruses into cells. However, little is known about how lipid phase heterogeneity contributes to viral entry because of the fine-grained and still poorly understood complexity of biological membranes. We used model systems...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1800
更新日期:2015-06-01 00:00:00
abstract::Nature is a diverse and rich source of bioactive pathways or novel building blocks for synthetic biology. In this Perspective, we describe the emerging research field in which metagenomes are functionally interrogated using synthetic biology. This approach substantially expands the set of identified biological activit...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/s41589-018-0100-x
更新日期:2018-08-01 00:00:00
abstract::Hapalindole alkaloids are a structurally diverse class of cyanobacterial natural products defined by their varied polycyclic ring systems and diverse biological activities. These complex metabolites are generated from a common biosynthetic intermediate by the Stig cyclases in three mechanistic steps: a rare Cope rearr...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0003-x
更新日期:2018-04-01 00:00:00
abstract::Bacterial biofilms can be programmed to produce living materials with self-healing and evolvable functionalities. However, the wider use of artificial biofilms has been hindered by limitations on processability and functional protein secretion capacity. We describe a highly flexible and tunable living functional mater...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0169-2
更新日期:2019-01-01 00:00:00
abstract::Beyond established roles in collagen biosynthesis, hypoxic signaling and fatty acid metabolism, recent reports have now revealed roles for human 2-oxoglutarate-dependent oxygenases in histone and nucleic acid demethylation and in signaling protein hydroxylation. The emerging role of these oxygenases in enabling a mult...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio0308-152
更新日期:2008-03-01 00:00:00
abstract::Controlled distribution of lipids across various cell membranes is crucial for cell homeostasis and regulation. We developed an imaging method that allows simultaneous in situ quantification of cholesterol in two leaflets of the plasma membrane (PM) using tunable orthogonal cholesterol sensors. Our imaging revealed ma...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2268
更新日期:2017-03-01 00:00:00
abstract::Binding to the primary receptor, CD4, triggers conformational changes in the metastable HIV-1 envelope glycoprotein (Env) trimer ((gp120-gp41)3) that are important for virus entry into host cells. These changes include an 'opening' of the trimer, creation of a binding site for the CCR5 co-receptor and formation and/or...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1623
更新日期:2014-10-01 00:00:00
abstract::Methods to evolve synthetic, rather than biological, polymers could significantly expand the functional potential of polymers that emerge from in vitro evolution. Requirements for synthetic polymer evolution include (i) sequence-specific polymerization of synthetic building blocks on an amplifiable template, (ii) disp...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.280
更新日期:2010-02-01 00:00:00
abstract::F(1)-ATPase is an ATP-driven rotary motor protein in which the γ-subunit rotates against the catalytic stator ring. Although the reaction scheme of F(1) has mostly been revealed, the timing of inorganic phosphate (P(i)) release remains controversial. Here we addressed this issue by verifying the reversibility of ATP h...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.443
更新日期:2010-11-01 00:00:00
abstract::The serotonin6 receptor (5-HT6R) is a promising target for treating cognitive deficits of schizophrenia often linked to alterations of neuronal development. This receptor controls neurodevelopmental processes, but the signaling mechanisms involved remain poorly understood. Using a proteomic strategy, we show that 5-HT...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1547
更新日期:2014-07-01 00:00:00
abstract::The nematode Caenorhabditis elegans requires exogenous cholesterol to survive and its depletion leads to early developmental arrest. Thus, tight regulation of cholesterol storage and distribution within the organism is indispensable. Here, we present a novel class of C. elegans phosphorylated glycosphingolipids, phosp...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2347
更新日期:2017-06-01 00:00:00
abstract::Accumulation of unfolded proteins within the endoplasmic reticulum (ER) of eukaryotic cells leads to an unfolded protein response (UPR) that either restores homeostasis or commits the cells to apoptosis. Tools traditionally used to study the UPR are proapoptotic and thus confound analysis of long-term cellular respons...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1638
更新日期:2014-11-01 00:00:00
abstract::Actin filament dynamics are critical in cell motility. The structure of actin filament changes spontaneously and can also be regulated by actin-binding proteins, allowing actin to readily function in response to external stimuli. The interaction with the motor protein myosin changes the dynamic nature of actin filamen...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio763
更新日期:2006-02-01 00:00:00
abstract::Enzyme-catalyzed peptide ligation is a powerful tool for site-specific protein bioconjugation, but stringent enzyme-substrate specificity limits its utility. We developed an approach for comprehensively characterizing peptide ligase specificity for N termini using proteome-derived peptide libraries. We used this strat...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2521
更新日期:2018-01-01 00:00:00
abstract::Identifying targets of antibacterial compounds remains a challenging step in the development of antibiotics. We have developed a two-pronged functional genomics approach to predict mechanism of action that uses mutant fitness data from antibiotic-treated transposon libraries containing both upregulation and inactivati...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0041-4
更新日期:2018-06-01 00:00:00
abstract::SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor (D2R), but it contains structural features associated with orthosteric D2R antagonists. Using a functional complementation system to control the identity of individual protomers within a dimeric D2R complex, we converted ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1593
更新日期:2014-09-01 00:00:00
abstract::The function of many biologically active molecules requires the presence of carbon-nitrogen bonds in strategic positions. The biosynthetic pathways leading to such bonds can be bypassed through chemical synthesis to synthesize natural products more efficiently and also to generate the molecular diversity unavailable i...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio0606-284
更新日期:2006-06-01 00:00:00
abstract::The MerR-family transcription factors (TFs) are a large group of bacterial proteins responding to cellular metal ions and multiple antibiotics by binding within central RNA polymerase-binding regions of a promoter. While most TFs alter transcription through protein-protein interactions, MerR TFs are capable of reshapi...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-00653-x
更新日期:2021-01-01 00:00:00
abstract::Kinase inhibitors are important cancer drugs, but they tend to display limited target specificity, and their target profiles are often challenging to rationalize in terms of molecular mechanism. Here we report that the clinical kinase inhibitor bosutinib recognizes its kinase targets by engaging a pair of conserved st...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1404
更新日期:2014-02-01 00:00:00
abstract::Specific chemicals can prime the plant immune system for augmented defense. β-aminobutyric acid (BABA) is a priming agent that provides broad-spectrum disease protection. However, BABA also suppresses plant growth when applied in high doses, which has hampered its application as a crop defense activator. Here we descr...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1520
更新日期:2014-06-01 00:00:00
abstract::Chemical biology is an interdisciplinary field that is undergoing rapid expansion around the globe. Recently, the Japanese Society for Chemical Biology sponsored its inaugural scientific meeting to discuss research at the interface of chemistry and biology. ...
journal_title:Nature chemical biology
pub_type:
doi:10.1038/nchembio0806-392
更新日期:2006-08-01 00:00:00
abstract::Many protein kinases are key nodal signaling molecules that regulate a wide range of cellular functions. These functions may require complex spatiotemporal regulation of kinase activities. Here, we show that protein kinase A (PKA), Ca(2+) and cyclic AMP (cAMP) oscillate in sync in insulin-secreting MIN6 beta cells, fo...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.478
更新日期:2011-01-01 00:00:00
abstract::Nonribosomal peptide antibiotics, including polymyxin, vancomycin, and teixobactin, most of which contain D-amino acids, are highly effective against multidrug-resistant bacteria. However, overusing antibiotics while ignoring the risk of resistance arising has inexorably led to widespread emergence of resistant bacter...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0009-4
更新日期:2018-04-01 00:00:00
abstract::Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1817
更新日期:2015-07-01 00:00:00