A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate.

abstract：:Only 25% of bacterial membrane transporters have functional annotation owing to the difficulty of experimental study and of accurate prediction of their function. Here we report a sequence-independent method for high-throughput mining of novel transporters. The method is based on ligand-responsive biosensor systems th...

journal_title：Nature chemical biology

authors： Genee HJ,Bali AP,Petersen SD,Siedler S,Bonde MT,Gronenberg LS,Kristensen M,Harrison SJ,Sommer MO

更新日期：2016-12-01 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

authors： Newmister SA,Li S,Garcia-Borràs M,Sanders JN,Yang S,Lowell AN,Yu F,Smith JL,Williams RM,Houk KN,Sherman DH

更新日期：2018-04-01 00:00:00

abstract：:The N-end rule pathway senses the N-terminal destabilizing residues of degradation substrates for the ubiquitin-proteasome system, whose integrity shields against various human syndromes including cancer and cardiovascular diseases. GID4, a subunit of the ubiquitin ligase GID complex, has been recently identified as t...

journal_title：Nature chemical biology

authors： Dong C,Zhang H,Li L,Tempel W,Loppnau P,Min J

更新日期：2018-05-01 00:00:00

abstract：:The GATOR1 (SEACIT) complex consisting of Iml1-Npr2-Npr3 inhibits target of rapamycin complex 1 (TORC1) in response to amino acid insufficiency. In glucose medium, Saccharomyces cerevisiae mutants lacking the function of this complex grow poorly in the absence of amino acid supplementation, despite showing hallmarks o...

journal_title：Nature chemical biology

authors： Chen J,Sutter BM,Shi L,Tu BP

更新日期：2017-11-01 00:00:00

abstract：:Enzymes that use the cofactor thiamin diphosphate (ThDP, 1), the biologically active form of vitamin B(1), are involved in numerous metabolic pathways in all organisms. Although a theory of the cofactor's underlying reaction mechanism has been established over the last five decades, the three-dimensional structures of...

journal_title：Nature chemical biology

authors： Wille G,Meyer D,Steinmetz A,Hinze E,Golbik R,Tittmann K

更新日期：2006-06-01 00:00:00

abstract：:Improving the control of energy homeostasis can lower cardiovascular risk in metabolically compromised individuals. To identify new regulators of whole-body energy control, we conducted a high-throughput screen in transgenic reporter zebrafish for small molecules that modulate the expression of the fasting-inducible g...

journal_title：Nature chemical biology

authors： Gut P,Baeza-Raja B,Andersson O,Hasenkamp L,Hsiao J,Hesselson D,Akassoglou K,Verdin E,Hirschey MD,Stainier DY

更新日期：2013-02-01 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

authors： Santiago M,Lee W,Fayad AA,Coe KA,Rajagopal M,Do T,Hennessen F,Srisuknimit V,Müller R,Meredith TC,Walker S

更新日期：2018-06-01 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

authors： Leidecker O,Bonfiglio JJ,Colby T,Zhang Q,Atanassov I,Zaja R,Palazzo L,Stockum A,Ahel I,Matic I

更新日期：2016-12-01 00:00:00

abstract：:Despite the remarkable versatility displayed by flavin-dependent monooxygenases (FMOs) in natural product biosynthesis, one notably missing activity is the oxidative generation of carbonate functional groups. We describe a multifunctional Baeyer-Villiger monooxygenase, CcsB, which catalyzes the formation of an in-line...

journal_title：Nature chemical biology

authors： Hu Y,Dietrich D,Xu W,Patel A,Thuss JA,Wang J,Yin WB,Qiao K,Houk KN,Vederas JC,Tang Y

更新日期：2014-07-01 00:00:00

abstract：:Mitochondrial electron transport drives ATP synthesis but also generates reactive oxygen species, which are both cellular signals and damaging oxidants. Superoxide production by respiratory complex III is implicated in diverse signaling events and pathologies, but its role remains controversial. Using high-throughput ...

journal_title：Nature chemical biology

authors： Orr AL,Vargas L,Turk CN,Baaten JE,Matzen JT,Dardov VJ,Attle SJ,Li J,Quackenbush DC,Goncalves RL,Perevoshchikova IV,Petrassi HM,Meeusen SL,Ainscow EK,Brand MD

更新日期：2015-11-01 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

authors： Kozuka J,Yokota H,Arai Y,Ishii Y,Yanagida T

更新日期：2006-02-01 00:00:00

abstract：:Bile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes by binding to host receptors. There is an unmet need for a potent tool to inhibit BSHs across all gut bacteria ...

journal_title：Nature chemical biology

authors： Adhikari AA,Seegar TCM,Ficarro SB,McCurry MD,Ramachandran D,Yao L,Chaudhari SN,Ndousse-Fetter S,Banks AS,Marto JA,Blacklow SC,Devlin AS

更新日期：2020-03-01 00:00:00

abstract：:The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the crystal structure of inhibitor-bound hFEN1, which shows a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three ...

journal_title：Nature chemical biology

authors： Exell JC,Thompson MJ,Finger LD,Shaw SJ,Debreczeni J,Ward TA,McWhirter C,Siöberg CL,Martinez Molina D,Abbott WM,Jones CD,Nissink JW,Durant ST,Grasby JA

更新日期：2016-10-01 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

authors： Raina K,Noblin DJ,Serebrenik YV,Adams A,Zhao C,Crews CM

更新日期：2014-11-01 00:00:00

abstract：:The catalytic activity of many protein kinases is controlled by conformational changes of a conserved Asp-Phe-Gly (DFG) motif. We used an infrared probe to track the DFG motif of the mitotic kinase Aurora A (AurA) and found that allosteric activation by the spindle-associated protein Tpx2 involves an equilibrium shift...

journal_title：Nature chemical biology

authors： Cyphers S,Ruff EF,Behr JM,Chodera JD,Levinson NM

更新日期：2017-04-01 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

authors： Loenarz C,Schofield CJ

更新日期：2008-03-01 00:00:00

abstract：:Enzymatic incorporation of a halogen atom is a common feature in the biosyntheses of more than 4,500 natural products. Halogenation of unactivated carbon centers in the biosyntheses of several compounds of nonribosomal peptide origin is carried out by a class of mononuclear nonheme iron enzymes that require alpha-keto...

journal_title：Nature chemical biology

authors： Galonić DP,Barr EW,Walsh CT,Bollinger JM Jr,Krebs C

更新日期：2007-02-01 00:00:00

abstract：:The molecular forces that drive structural transitions between the open and closed states of channels and transporters are not well understood. The gate of the OmpA channel is formed by the central Glu52-Arg138 salt bridge, which can open to form alternate ion pairs with Lys82 and Glu128. To gain deeper insight into t...

journal_title：Nature chemical biology

authors： Hong H,Szabo G,Tamm LK

更新日期：2006-11-01 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

authors： Herschhorn A,Gu C,Espy N,Richard J,Finzi A,Sodroski JG

更新日期：2014-10-01 00:00:00

abstract：:Proper gene expression is essential for the survival of every cell. Once thought to be a passive transporter of genetic information, RNA has recently emerged as a key player in nearly every pathway in the cell. A full description of its structure is critical to understanding RNA function. Decades of research have focu...

journal_title：Nature chemical biology

authors： Kubota M,Tran C,Spitale RC

更新日期：2015-12-01 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

authors： Weeks AM,Wells JA

更新日期：2018-01-01 00:00:00

abstract：:Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for...

journal_title：Nature chemical biology

authors： Larsen JB,Jensen MB,Bhatia VK,Pedersen SL,Bjørnholm T,Iversen L,Uline M,Szleifer I,Jensen KJ,Hatzakis NS,Stamou D

更新日期：2015-03-01 00:00:00

abstract：:Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show that the G-quadruplex-interacting drug pyridostatin promotes growth arr...

journal_title：Nature chemical biology

authors： Rodriguez R,Miller KM,Forment JV,Bradshaw CR,Nikan M,Britton S,Oelschlaegel T,Xhemalce B,Balasubramanian S,Jackson SP

更新日期：2012-02-05 00:00:00

abstract：:Ferroptosis is a form of regulated necrotic cell death controlled by glutathione peroxidase 4 (GPX4). At present, mechanisms that could predict sensitivity and/or resistance and that may be exploited to modulate ferroptosis are needed. We applied two independent approaches-a genome-wide CRISPR-based genetic screen and...

journal_title：Nature chemical biology

authors： Doll S,Proneth B,Tyurina YY,Panzilius E,Kobayashi S,Ingold I,Irmler M,Beckers J,Aichler M,Walch A,Prokisch H,Trümbach D,Mao G,Qu F,Bayir H,Füllekrug J,Scheel CH,Wurst W,Schick JA,Kagan VE,Angeli JP,Conrad M

更新日期：2017-01-01 00:00:00

abstract：:The ykkC family of bacterial riboswitches combines several widespread classes that have similar secondary structures and consensus motifs but control different genes in response to different cellular metabolites. Here we report the crystal structures of two distinct ykkC riboswitches specifically bound to their cognat...

journal_title：Nature chemical biology

authors： Peselis A,Serganov A

更新日期：2018-09-01 00:00:00

abstract：:Mammals that degrade uric acid are not affected by gout or urate kidney stones. It is not fully understood how they convert uric acid into the much more soluble allantoin. Until recently, it had long been thought that urate oxidase was the only enzyme responsible for this conversion. However, detailed studies of the m...

journal_title：Nature chemical biology

authors： Ramazzina I,Folli C,Secchi A,Berni R,Percudani R

更新日期：2006-03-01 00:00:00

abstract：: ...

journal_title：Nature chemical biology

authors： Deane C

更新日期：2018-06-01 00:00:00

abstract：:Targeted protein degradation via small-molecule modulation of cereblon offers vast potential for the development of new therapeutics. Cereblon-binding therapeutics carry the safety risks of thalidomide, which caused an epidemic of severe birth defects characterized by forelimb shortening or phocomelia. Here we show th...

journal_title：Nature chemical biology

authors： Matyskiela ME,Couto S,Zheng X,Lu G,Hui J,Stamp K,Drew C,Ren Y,Wang M,Carpenter A,Lee CW,Clayton T,Fang W,Lu CC,Riley M,Abdubek P,Blease K,Hartke J,Kumar G,Vessey R,Rolfe M,Hamann LG,Chamberlain PP

更新日期：2018-10-01 00:00:00

abstract：:Post-transcriptional RNA modifications can be dynamic and might have functions beyond fine-tuning the structure and function of RNA. Understanding these RNA modification pathways and their functions may allow researchers to identify new layers of gene regulation at the RNA level. ...

journal_title：Nature chemical biology

authors： He C

更新日期：2010-12-01 00:00:00

abstract：:Nontranslational functions of vertebrate aminoacyl tRNA synthetases (aaRSs), which catalyze the production of aminoacyl-tRNAs for protein synthesis, have recently been discovered. Although these new functions were thought to be 'moonlighting activities', many are as critical for cellular homeostasis as their activity ...

journal_title：Nature chemical biology

authors： Guo M,Schimmel P

更新日期：2013-03-01 00:00:00