The role of distant mutations and allosteric regulation on LovD active site dynamics.

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

authors： Fang C,Philips SJ,Wu X,Chen K,Shi J,Shen L,Xu J,Feng Y,O'Halloran TV,Zhang Y

更新日期：2021-01-01 00:00:00

abstract：:Small molecules that specifically activate an intracellular protein of interest are highly desirable. A generally applicable strategy, however, remains elusive. Herein we describe a small molecule-triggered bioorthogonal protein decaging technique that relies on the inverse electron-demand Diels-Alder reaction for eli...

journal_title：Nature chemical biology

authors： Li J,Jia S,Chen PR

更新日期：2014-12-01 00:00:00

abstract：:What do organic synthesis, mechanistic enzymology, structural biology and glycoscience have in common? They all span chemistry and biology, benefit from and contribute to multidisciplinary approaches, and were up for discussion at a recent symposium in Dublin. ...

journal_title：Nature chemical biology

authors： Murphy PV,Rutledge PJ

更新日期：2006-02-01 00:00:00

abstract：:Here we identify the amino acid transporter AnsP1 as the unique aspartate importer in the human pathogen Mycobacterium tuberculosis. Metabolomic analysis of a mutant with an inactive AnsP1 revealed that the transporter is essential for M. tuberculosis to assimilate nitrogen from aspartate. Virulence of the AnsP1 mutan...

journal_title：Nature chemical biology

authors： Gouzy A,Larrouy-Maumus G,Wu TD,Peixoto A,Levillain F,Lugo-Villarino G,Guerquin-Kern JL,de Carvalho LP,Poquet Y,Neyrolles O

更新日期：2013-11-01 00:00:00

abstract：:Improved methods for studying intracellular reactive Fe(II) are of significant interest for studies of iron metabolism and disease-relevant changes in iron homeostasis. Here we describe a highly selective reactivity-based probe in which a Fenton-type reaction with intracellular labile Fe(II) leads to unmasking of the ...

journal_title：Nature chemical biology

authors： Spangler B,Morgan CW,Fontaine SD,Vander Wal MN,Chang CJ,Wells JA,Renslo AR

更新日期：2016-09-01 00:00:00

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

authors： Hillwig ML,Liu X

更新日期：2014-11-01 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

authors： DeLoache WC,Russ ZN,Narcross L,Gonzales AM,Martin VJ,Dueber JE

更新日期：2015-07-01 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：:In response to decreasing Ca2+ levels in the endoplasmic reticulum, STIM proteins couple with Orai channels in the plasma membrane, leading to Ca2+ influx into the cell. In addition to Ca2+-related endoplasmic reticulum stress, STIM proteins are emerging as general stress sensors that react to multiple stress signals ...

journal_title：Nature chemical biology

authors： Soboloff J,Madesh M,Gill DL

更新日期：2011-07-18 00:00:00

abstract：:We identify an Arabidopsis pyridoxal-phosphate-dependent aminotransferase, VAS1, whose loss-of-function simultaneously increases amounts of the phytohormone auxin and the ethylene precursor 1-aminocyclopropane-1-carboxylate. VAS1 uses the ethylene biosynthetic intermediate methionine as an amino donor and the auxin bi...

journal_title：Nature chemical biology

authors： Zheng Z,Guo Y,Novák O,Dai X,Zhao Y,Ljung K,Noel JP,Chory J

更新日期：2013-04-01 00:00:00

abstract：:Helical membrane proteins are typically assumed to attain stable transmembrane topologies immediately upon co-translational membrane insertion. Here we show that unassembled monomers of the small multidrug resistance (SMR) family exist in a dynamic equilibrium where the N-terminal transmembrane helix flips in and out ...

journal_title：Nature chemical biology

authors： Seurig M,Ek M,von Heijne G,Fluman N

更新日期：2019-10-01 00:00:00

abstract：:The phytohormone auxin indole-3-acetic acid (IAA) regulates nearly all aspects of plant growth and development. Despite substantial progress in our understanding of auxin biology, delineating specific auxin response remains a major challenge. Auxin regulates transcriptional response via its receptors, TIR1 and AFB F-b...

journal_title：Nature chemical biology

authors： Uchida N,Takahashi K,Iwasaki R,Yamada R,Yoshimura M,Endo TA,Kimura S,Zhang H,Nomoto M,Tada Y,Kinoshita T,Itami K,Hagihara S,Torii KU

更新日期：2018-03-01 00:00:00

abstract：:Lysostaphin is a bacteriolytic enzyme targeting peptidoglycan, the essential component of the bacterial cell envelope. It displays a very potent and specific activity toward staphylococci, including methicillin-resistant Staphylococcus aureus. Lysostaphin causes rapid cell lysis and disrupts biofilms, and is therefore...

journal_title：Nature chemical biology

authors： Gonzalez-Delgado LS,Walters-Morgan H,Salamaga B,Robertson AJ,Hounslow AM,Jagielska E,Sabała I,Williamson MP,Lovering AL,Mesnage S

更新日期：2020-01-01 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

authors： Lane JR,Donthamsetti P,Shonberg J,Draper-Joyce CJ,Dentry S,Michino M,Shi L,López L,Scammells PJ,Capuano B,Sexton PM,Javitch JA,Christopoulos A

更新日期：2014-09-01 00:00:00

abstract：:Plants have recently moved into the spotlight owing to the growing realization that the world needs solutions to energy and food production that are sustainable and environmentally sound. Iron, copper and zinc are essential for plant growth and development, yet the same properties that make these transition metals ind...

journal_title：Nature chemical biology

authors： Palmer CM,Guerinot ML

更新日期：2009-05-01 00:00:00

abstract：:The With-No-Lysine (K) (WNK) kinases play a critical role in blood pressure regulation and body fluid and electrolyte homeostasis. Herein, we introduce the first orally bioavailable pan-WNK-kinase inhibitor, WNK463, that exploits unique structural features of the WNK kinases for both affinity and kinase selectivity. I...

journal_title：Nature chemical biology

authors： Yamada K,Park HM,Rigel DF,DiPetrillo K,Whalen EJ,Anisowicz A,Beil M,Berstler J,Brocklehurst CE,Burdick DA,Caplan SL,Capparelli MP,Chen G,Chen W,Dale B,Deng L,Fu F,Hamamatsu N,Harasaki K,Herr T,Hoffmann P,Hu QY,

更新日期：2016-11-01 00:00:00

abstract：:Polyglutamine (polyQ) stretches exceeding a threshold length confer a toxic function to proteins that contain them and cause at least nine neurological disorders. The basis for this toxicity threshold is unclear. Although polyQ expansions render proteins prone to aggregate into inclusion bodies, this may be a neuronal...

journal_title：Nature chemical biology

authors： Miller J,Arrasate M,Brooks E,Libeu CP,Legleiter J,Hatters D,Curtis J,Cheung K,Krishnan P,Mitra S,Widjaja K,Shaby BA,Lotz GP,Newhouse Y,Mitchell EJ,Osmand A,Gray M,Thulasiramin V,Saudou F,Segal M,Yang XW,Masliah

更新日期：2011-10-30 00:00:00

abstract：:MicroRNAs are evolutionarily conserved small, noncoding RNAs that regulate diverse biological processes. Due to their essential regulatory roles, microRNA biogenesis is tightly regulated, where protein factors are often found to interact with specific primary and precursor microRNAs for regulation. Here, using NMR rel...

journal_title：Nature chemical biology

authors： Baisden JT,Boyer JA,Zhao B,Hammond SM,Zhang Q

更新日期：2021-01-01 00:00:00

abstract：:Jasmonates are lipid-derived plant hormones that regulate plant defenses and numerous developmental processes. Although the biosynthesis and molecular function of the most active form of the hormone, (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile), have been unraveled, it remains poorly understood how the diversity of bioac...

journal_title：Nature chemical biology

authors： Meesters C,Mönig T,Oeljeklaus J,Krahn D,Westfall CS,Hause B,Jez JM,Kaiser M,Kombrink E

更新日期：2014-10-01 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

authors： Ni Q,Ganesan A,Aye-Han NN,Gao X,Allen MD,Levchenko A,Zhang J

更新日期：2011-01-01 00:00:00

abstract：:Subtilosin A is a 35-residue, ribosomally synthesized bacteriocin encoded by the sbo-alb operon of Bacillus subtilis. It is composed of a head-to-tail circular peptide backbone that is additionally restrained by three unusual thioether bonds between three cysteines and the α-carbon of one threonine and two phenylalani...

journal_title：Nature chemical biology

authors： Flühe L,Knappe TA,Gattner MJ,Schäfer A,Burghaus O,Linne U,Marahiel MA

更新日期：2012-02-26 00:00:00

abstract：:Regulation of gene expression in response to the changing environment is critical for cell survival. For instance, binding of macrolide antibiotics to the ribosome promotes translation arrest at the leader open reading frames ermCL and ermBL, which is necessary for inducing the antibiotic resistance genes ermC and erm...

journal_title：Nature chemical biology

authors： Gupta P,Liu B,Klepacki D,Gupta V,Schulten K,Mankin AS,Vázquez-Laslop N

更新日期：2016-03-01 00:00:00

abstract：:Liver X receptors (Lxrα and Lxrβ) are ligand-dependent nuclear receptors critical for ventral midbrain neurogenesis in vivo. However, no endogenous midbrain Lxr ligand has so far been identified. Here we used LC/MS and functional assays to identify cholic acid as a new Lxr ligand. Moreover, 24(S),25-epoxycholesterol (...

journal_title：Nature chemical biology

authors： Theofilopoulos S,Wang Y,Kitambi SS,Sacchetti P,Sousa KM,Bodin K,Kirk J,Saltó C,Gustafsson M,Toledo EM,Karu K,Gustafsson JÅ,Steffensen KR,Ernfors P,Sjövall J,Griffiths WJ,Arenas E

更新日期：2013-02-01 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：:Naphthalene (1) and para-dichlorobenzene (PDCB, 2), which are widely used as moth repellents and air fresheners, cause cancer in rodents and are potential human carcinogens. However, their mechanisms of action remain unclear. Here we describe a novel method for delivering and screening hydrophobic chemicals in C. eleg...

journal_title：Nature chemical biology

authors： Kokel D,Li Y,Qin J,Xue D

更新日期：2006-06-01 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：: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

authors： Tarrant MK,Rho HS,Xie Z,Jiang YL,Gross C,Culhane JC,Yan G,Qian J,Ichikawa Y,Matsuoka T,Zachara N,Etzkorn FA,Hart GW,Jeong JS,Blackshaw S,Zhu H,Cole PA

更新日期：2012-01-22 00:00:00

abstract：:Phosphorylation and glycosylation of the tau protein, which is implicated in neurodegenerative diseases, are intimately linked. In vivo pharmacological inhibition of tau deglycosylation may be a new way to suppress abnormal tau phosphorylation, known to be involved in the formation of neurofibrillary tangles in the br...

journal_title：Nature chemical biology

authors： Fischer PM

更新日期：2008-08-01 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

authors： Olson CM,Jiang B,Erb MA,Liang Y,Doctor ZM,Zhang Z,Zhang T,Kwiatkowski N,Boukhali M,Green JL,Haas W,Nomanbhoy T,Fischer ES,Young RA,Bradner JE,Winter GE,Gray NS

更新日期：2018-02-01 00:00:00

abstract：:Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoy...

journal_title：Nature chemical biology

authors： Kathayat RS,Elvira PD,Dickinson BC

更新日期：2017-02-01 00:00:00