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 of increased TORC1 signaling. Such mutants sense that they are amino acid replete and thus repress metabolic activities that are important for achieving this state. We found that npr2Δ mutants have defective mitochondrial tricarboxylic acid (TCA)-cycle activity and retrograde response. Supplementation with glutamine, and especially aspartate, which are nitrogen-containing forms of TCA-cycle intermediates, rescues growth of npr2Δ mutants. These amino acids are then consumed in biosynthetic pathways that require nitrogen to support proliferative metabolism. Our findings revealed that negative regulators of TORC1, such as GATOR1 (SEACIT), regulate the cataplerotic synthesis of these amino acids from the TCA cycle, in tune with the amino acid and nitrogen status of cells.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Chen J,Sutter BM,Shi L,Tu BPdoi
10.1038/nchembio.2478subject
Has Abstractpub_date
2017-11-01 00:00:00pages
1179-1186issue
11eissn
1552-4450issn
1552-4469pii
nchembio.2478journal_volume
13pub_type
杂志文章abstract：:Regio- and stereospecific incorporation of a halogen atom to an unactivated sp(3) carbon in a freestanding molecule is a challenging transformation that is currently missing in the inventory of enzyme-mediated reactions. Here we report what is to our knowledge the first example of a nonheme iron enzyme (WelO5) in the ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1625
更新日期：2014-11-01 00:00:00
abstract：:Occurrence of the BCR-ABL(T315I) gatekeeper mutation is among the most pressing challenges in the therapy of chronic myeloid leukemia (CML). Several BCR-ABL inhibitors have multiple targets and pleiotropic effects that could be exploited for their synergistic potential. Testing combinations of such kinase inhibitors i...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1085
更新日期：2012-11-01 00:00:00
abstract：:In eukaryotes, cytosolic monothiol glutaredoxins are proteins implicated in intracellular iron trafficking and sensing via their bound [2Fe-2S] clusters. We define a new role of human cytosolic monothiol glutaredoxin-3 (GRX3) in transferring its [2Fe-2S] clusters to human anamorsin, a physical and functional protein p...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1892
更新日期：2015-10-01 00:00:00
abstract：:Sulfoquinovose is produced by photosynthetic organisms at a rate of 10(10) tons per annum and is degraded by bacteria as a source of carbon and sulfur. We have identified Escherichia coli YihQ as the first dedicated sulfoquinovosidase and the gateway enzyme to sulfoglycolytic pathways. Structural and mutagenesis studi...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2023
更新日期：2016-04-01 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
pub_type： 杂志文章
doi：10.1038/nchembio788
更新日期：2006-06-01 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：:Higher plants resist the forces of gravity and powerful lateral forces through the cumulative strength of the walls that surround individual cells. These walls consist mainly of cellulose, noncellulosic polysaccharides and lignin, in proportions that depend upon the specific functions of the cell and its stage of deve...
journal_title：Nature chemical biology
pub_type： 杂志文章,评审
doi：10.1038/nchembio.439
更新日期：2010-10-01 00:00:00
abstract：: ...
journal_title：Nature chemical biology
pub_type： 评论,杂志文章
doi：10.1038/s41589-018-0199-9
更新日期：2019-01-01 00:00:00
abstract：:Benzylisoquinoline alkaloids (BIAs) are a diverse family of plant-specialized metabolites that include the pharmaceuticals codeine and morphine and their derivatives. Microbial synthesis of BIAs holds promise as an alternative to traditional crop-based manufacturing. Here we demonstrate the production of the key BIA i...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1816
更新日期：2015-07-01 00:00:00
abstract：:Although metabolic networks have been reconstructed on a genome scale, the corresponding reconstruction and integration of governing transcriptional regulatory networks has not been fully achieved. Here we reconstruct such an integrated network for amino acid metabolism in Escherichia coli. Analysis of ChIP-chip and g...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.710
更新日期：2011-11-13 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：:Nitric oxide (NO) signaling through the formation of cGMP is well established; however, there seems to be an increasing role for cGMP-independent NO signaling. Although key molecular details remain unanswered, S-nitrosation represents an example of cGMP-independent NO signaling. This modification has garnered recent a...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio720
更新日期：2005-08-01 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：:Methods for imaging and tracking single molecules conjugated with fluorescent probes, called single-molecule tracking (SMT), are now providing researchers with the unprecedented ability to directly observe molecular behaviors and interactions in living cells. Current SMT methods are achieving almost the ultimate spati...
journal_title：Nature chemical biology
pub_type： 杂志文章,评审
doi：10.1038/nchembio.1558
更新日期：2014-07-01 00:00:00
abstract：:The potential utility of synthetic macrocycles (MCs) as drugs, particularly against low-druggability targets such as protein-protein interactions, has been widely discussed. There is little information, however, to guide the design of MCs for good target protein-binding activity or bioavailability. To address this kno...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1584
更新日期：2014-09-01 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
pub_type： 杂志文章
doi：10.1038/nchembio856
更新日期：2007-02-01 00:00:00
abstract：:The P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, bu...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1863
更新日期：2015-09-01 00:00:00
abstract：:The streptothricin (ST) antibiotics, produced by Streptomyces bacteria, contain L-β-lysine ((3S)-3,6-diaminohexanoic acid) oligopeptides as pendant chains. Here we describe three unusual nonribosomal peptide synthetases (NRPSs) involved in ST biosynthesis: ORF 5 (a stand-alone adenylation (A) domain), ORF 18 (containi...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1040
更新日期：2012-09-01 00:00:00
abstract：:Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2380
更新日期：2017-07-01 00:00:00
abstract：:Thiazole/oxazole-modified microcins (TOMMs) encompass a recently defined class of ribosomally synthesized natural products with a diverse set of biological activities. Although TOMM biosynthesis has been investigated for over a decade, the mechanism of heterocycle formation by the synthetase enzymes remains poorly und...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.944
更新日期：2012-04-22 00:00:00
abstract：:Secondary structure refolding is a key event in biology as it modulates the conformation of many proteins in the cell, generating functional or aberrant states. The crystal structures of mannosyltransferase PimA reveal an exceptional flexibility of the protein along the catalytic cycle, including β-strand-to-α-helix a...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1694
更新日期：2015-01-01 00:00:00
abstract：:Bifunctional Rel stringent factors, the most abundant class of RelA/SpoT homologs, are ribosome-associated enzymes that transfer a pyrophosphate from ATP onto the 3' of guanosine tri-/diphosphate (GTP/GDP) to synthesize the bacterial alarmone (p)ppGpp, and also catalyze the 3' pyrophosphate hydrolysis to degrade it. T...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-020-0520-2
更新日期：2020-08-01 00:00:00
abstract：:Kinetochores act as hubs for multiple activities during cell division, including microtubule interactions and spindle checkpoint signaling. Each kinetochore can act autonomously, and activities change rapidly as proteins are recruited to, or removed from, kinetochores. Understanding this dynamic system requires tools ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2456
更新日期：2017-10-01 00:00:00
abstract：:Targeted drugs are effective when they directly inhibit strong disease drivers, but only a small fraction of diseases feature defined actionable drivers. Alternatively, network-based approaches can uncover new therapeutic opportunities. Applying an integrated phenotypic screening, chemical and phosphoproteomics strate...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2489
更新日期：2017-12-01 00:00:00
abstract：:Thioredoxin (Trx) is one of the two major thiol antioxidants, playing essential roles in redox homeostasis and signaling. Despite its importance, there is a lack of methods for monitoring Trx redox dynamics in live cells, hindering a better understanding of physiological and pathological roles of the Trx redox system....
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2417
更新日期：2017-09-01 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：:RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy, footprinting of long 7-deazaguanine-su...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2228
更新日期：2017-01-01 00:00:00
abstract：:In this study, we demonstrate the feasibility of expanding the genetic code of Escherichia coli using its own tryptophanyl-tRNA synthetase and tRNA (TrpRS-tRNATrp) pair. This was made possible by first functionally replacing this endogenous pair with an E. coli-optimized counterpart from Saccharomyces cerevisiae, and ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2312
更新日期：2017-04-01 00:00:00
abstract：:To maximize a desired product, metabolic engineers typically express enzymes to high, constant levels. Yet, permanent pathway activation can have undesirable consequences including competition with essential pathways and accumulation of toxic intermediates. Faced with similar challenges, natural metabolic systems comp...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-019-0284-8
更新日期：2019-06-01 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
