当前位置： SCI文献检索 > MOLECULAR PHARMACOLOGY期刊下所有文献 > Inhibition of branched-chain alpha-keto acid dehydrogenase kinase and Sln1 yeast histidine kinase by the antifungal antibiotic radicicol.

Inhibition of branched-chain alpha-keto acid dehydrogenase kinase and Sln1 yeast histidine kinase by the antifungal antibiotic radicicol.

Abstract：

:The 90-kDa heat shock family (HSP90) of protein and two-component histidine kinases, although quite distinct at the primary amino acid sequence level, share a common structural ATP-binding domain known as the Bergerat fold. The Bergerat fold is important for the ATPase activity and associated chaperone function of HSP90. Two-component histidine kinases occur in bacteria, yeast, and plants but have yet to be identified in mammalian cells. The antifungal antibiotic radicicol (Monorden) has been shown to bind to the Bergerat fold of HSP90 and to inhibit its ATPase activity. The structural similarity between the Bergerat fold of HSP90 and bacterial two-component histidine kinases prompted our inquiry into whether radicicol could be a potential inhibitor of histidine kinase-like proteins. Structural homology searches suggest that the ATP-binding domains of the yeast histidine kinase Sln1 and the mammalian, branched-chain alpha-keto acid dehydrogenase kinase are very similar to that of other Bergerat fold family members. On the basis of structural homology, we tested radicicol as a potential inhibitor of Sln1 and branched-chain alpha-keto acid dehydrogenase kinase (BCKDHK) and propose a mechanism of inhibition of these kinases. Although BCKDHK has been shown to have serine autophosphorylation activity, we speculate, based on the results from this study and other supporting evidence, that BCKDHK may also have intrinsic histidine kinase activity.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Besant PG,Lasker MV,Bui CD,Turck CW

doi

10.1124/mol.62.2.289

keywords:

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

289-96

issue

2

eissn

0026-895X

issn

1521-0111

journal_volume

62

pub_type

杂志文章

相关文献

MOLECULAR PHARMACOLOGY文献大全
  • Opioid Pharmacology under the Microscope.

    abstract：:The powerful analgesic effects of opioid drugs have captivated the interest of physicians and scientists for millennia, and the ability of opioid drugs to produce serious undesired effects has been recognized for a similar period of time (Kieffer and Evans, 2009). Many of these develop progressively with prolonged or ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章,评审

    doi：10.1124/mol.119.119321

    authors： Jullié D,Gondin AB,von Zastrow M,Canals M

    更新日期：2020-10-01 00:00:00

  • The inhibitory potency and selectivity of arginine substrate site nitric-oxide synthase inhibitors is solely determined by their affinity toward the different isoenzymes.

    abstract：:We have investigated various nitric oxide (NO) synthase inhibitors for their affinity and selectivity toward the three human isoenzymes in radioligand binding experiments. Therefore, we developed the new radioligand [(3)H]2-amino-4-picoline to measure binding of these compounds to the three human NO synthase (NOS) iso...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Boer R,Ulrich WR,Klein T,Mirau B,Haas S,Baur I

    更新日期：2000-11-01 00:00:00

  • Computational discovery of novel low micromolar human pregnane X receptor antagonists.

    abstract：:Very few antagonists have been identified for the human pregnane X receptor (PXR). These molecules may be of use for modulating the effects of therapeutic drugs, which are potent agonists for this receptor (e.g., some anticancer compounds and macrolide antibiotics), with subsequent effects on transcriptional regulatio...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.108.049437

    authors： Ekins S,Kholodovych V,Ai N,Sinz M,Gal J,Gera L,Welsh WJ,Bachmann K,Mani S

    更新日期：2008-09-01 00:00:00

  • Molecular basis for the selective interaction of synthetic agonists with the human histamine H1-receptor compared with the guinea pig H1-receptor.

    abstract：:Previous studies revealed that phenylhistamines and histaprodifens possess higher potency and affinity at guinea pig histamine H(1)-receptor (gpH(1)R) than at human histamine H(1)-receptor (hH(1)R). However, we recently identified an imidazolylpropylguanidine [N(1)-(3-cyclohexylbutanoyl)-N(2)-[3-(1H-imidazol-4-yl)-pro...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.108.053009

    authors： Strasser A,Wittmann HJ,Kunze M,Elz S,Seifert R

    更新日期：2009-03-01 00:00:00

  • Anticancer drug resistance induced by disruption of the Saccharomyces cerevisiae NPR2 gene: a novel component involved in cisplatin- and doxorubicin-provoked cell kill.

    abstract：:The therapeutic potential of antitumor drugs is seriously limited by the manifestation of cellular drug resistance. We used the budding yeast Saccharomyces cerevisiae as a model system to identify novel mechanisms of resistance to one of the most active anticancer agents, cisplatin. We pinpointed NPR2 (nitrogen permea...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.64.2.259

    authors： Schenk PW,Brok M,Boersma AW,Brandsma JA,Den Dulk H,Burger H,Stoter G,Brouwer J,Nooter K

    更新日期：2003-08-01 00:00:00

  • Enantioselective effects of hydroxy metabolites of bupropion on behavior and on function of monoamine transporters and nicotinic receptors.

    abstract：:Bupropion is an atypical antidepressant that also has usefulness as a smoking-cessation aid. Because hydroxybupropion, a major metabolite of bupropion, is believed to contribute to its antidepressant activity, this metabolite may also contribute to the smoking-cessation properties of bupropion. This study investigated...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.104.001313

    authors： Damaj MI,Carroll FI,Eaton JB,Navarro HA,Blough BE,Mirza S,Lukas RJ,Martin BR

    更新日期：2004-09-01 00:00:00

  • Expression profiling of ABC transporters in a drug-resistant breast cancer cell line using AmpArray.

    abstract：:ATP-binding cassette (ABC) membrane proteins comprise a superfamily of transporters with a wide variety of substrates. Humans have 49 members in this superfamily. Several human ABC transporters, such as ABCB1 and ABCC1, have been attributed to cause multidrug resistance (MDR) in cancer treatment when over-expressed. I...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.105.011015

    authors： Liu Y,Peng H,Zhang JT

    更新日期：2005-08-01 00:00:00

  • A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling.

    abstract：:Metabotropic glutamate receptor 5 (mGlu5) is a target for the treatment of central nervous system (CNS) disorders, such as schizophrenia and Alzheimer's disease. Furthermore, mGlu5 has been shown to play an important role in hippocampal synaptic plasticity, specifically in long-term depression (LTD) and long-term pote...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.112.082891

    authors： Noetzel MJ,Gregory KJ,Vinson PN,Manka JT,Stauffer SR,Lindsley CW,Niswender CM,Xiang Z,Conn PJ

    更新日期：2013-04-01 00:00:00

  • Prolonged ethanol inhalation decreases gamma-aminobutyric acidA receptor alpha subunit mRNAs in the rat cerebral cortex.

    abstract：:Ethanol administration to rats by ethanol vapor inhalation (14 days) results in a 40-50% reduction in the level of gamma-aminobutyric acidA (GABAA) receptor alpha 1 subunit mRNAs [4.4 and 4.8 kilobases (kb)] in the cerebral cortex. The level of alpha 2 subunit mRNA (8.0 kb) was also reduced by 29%, whereas there was n...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Montpied P,Morrow AL,Karanian JW,Ginns EI,Martin BM,Paul SM

    更新日期：1991-02-01 00:00:00

  • Formation of ADP-sensitive phosphorylated intermediate in the electric eel Na, K-ATPase preparation.

    abstract：:The ADP-sensitive and K+ -sensitive phosphorylated forms of Na,K-ATPase (E1P and E2P, respectively) are believed to be the main phosphorylated intermediates of Na,K-ATPase. In the presence of 100 mM Na+, E2P is the major component of the phosphorylated form in all native Na,K-ATPase preparations known, including the m...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Yoda A,Yoda S

    更新日期：1982-11-01 00:00:00

  • N-Phthalyl-l-Tryptophan (RG108), like Clozapine (CLO), Induces Chromatin Remodeling in Brains of Prenatally Stressed Mice.

    abstract：:Schizophrenia (SZ), schizoaffective (SZA), and bipolar (BP) disorder are neurodevelopmental psychopathological conditions related, in part, to genetic load and, in part, to environmentally induced epigenetic dysregulation of chromatin structure and function in neocortical GABAergic, glutamatergic, and monoaminergic ne...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.118.113415

    authors： Dong E,Locci V,Gatta E,Grayson DR,Guidotti A

    更新日期：2019-01-01 00:00:00

  • Relaxation of vascular and tracheal smooth muscle by cyclic nucleotide analogs that preferentially activate purified cGMP-dependent protein kinase.

    abstract：:Cyclic nucleotide analogs were used to study relaxation of pig coronary arteries and guinea pig tracheal smooth muscle in an attempt to determine the roles of cAMP- and cGMP-dependent protein kinases (cA-K and cG-K). In pig coronary artery strips, cGMP analogs were generally more effective than cAMP analogs in promoti...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Francis SH,Noblett BD,Todd BW,Wells JN,Corbin JD

    更新日期：1988-10-01 00:00:00

  • Guanethidine effects on the guinea pig vas deferens are antagonized by the blockers of calcium-activated potassium conductance, apamin, methylene blue, and quinine.

    abstract：:The blocking effects of guanethidine on electrically induced, neurally mediated, contractions of the guinea pig vas deferens in vitro could be markedly antagonized by the bee venom polypeptide apamin (20-60 nM), by 0.1 mM methylene blue, and (less regularly) by 0.1-0.15 mM quinine, three substances known to inhibit ca...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Stutzin A,Paravic F,Ormenño G,Orrego F

    更新日期：1983-03-01 00:00:00

  • Myristyl trimethyl ammonium bromide and octadecyl trimethyl ammonium bromide are surface-active small molecule dynamin inhibitors that block endocytosis mediated by dynamin I or dynamin II.

    abstract：:Dynamin is a GTPase enzyme involved in membrane constriction and fission during endocytosis. Phospholipid binding via its pleckstrin homology domain maximally stimulates dynamin activity. We developed a series of surface-active small-molecule inhibitors, such as myristyl trimethyl ammonium bromide (MiTMAB) and octadec...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.107.034207

    authors： Quan A,McGeachie AB,Keating DJ,van Dam EM,Rusak J,Chau N,Malladi CS,Chen C,McCluskey A,Cousin MA,Robinson PJ

    更新日期：2007-12-01 00:00:00

  • Picrate and niflumate block anion modulation of radioligand binding to the gamma-aminobutyric acid/benzodiazepine receptor complex.

    abstract：:The organic anions picrate (2,4,6-trinitrophenol) and niflumate (2-[[3-(trifluoromethyl)phenyl]-amino]-3-pyridinecarboxylate) were examined for their effects on radioligand binding to the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. Neither organic anion produced the enhancement of [35S] t-butylbicy...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Evoniuk G,Skolnick P

    更新日期：1988-12-01 00:00:00

  • Bezafibrate induces plasminogen activator inhibitor-1 gene expression in a CLOCK-dependent circadian manner.

    abstract：:A functional interaction between peroxisome proliferator-activated receptor alpha (PPARalpha) and components of the circadian clock has been suggested, but whether these transcriptional factors interact to regulate the expression of their target genes remains obscure. Here we used a PPARalpha ligand, bezafibrate, to s...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.110.064402

    authors： Oishi K,Koyanagi S,Matsunaga N,Kadota K,Ikeda E,Hayashida S,Kuramoto Y,Shimeno H,Soeda S,Ohdo S

    更新日期：2010-07-01 00:00:00

  • Differences in muscarinic receptor reserve for inhibition of adenylate cyclase and stimulation of phosphoinositide hydrolysis in chick heart cells.

    abstract：:Carbachol is 100 times more potent for inhibiting cyclic AMP formation than for stimulating phosphoinositide (PI) hydrolysis in chick heart cells. To determine whether this reflects differences in agonist affinity of the receptor(s) coupled to the two responses, we measured these functional responses following removal...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Brown JH,Goldstein D

    更新日期：1986-12-01 00:00:00

  • The kinetics of inhibition of human acetylcholinesterase and butyrylcholinesterase by two series of novel carbamates.

    abstract：:Controlled inhibition of brain acetyl- and butyrylcholinesterases (AChE and BChE, respectively) and of monoamine oxidase-B (MAO-B) may slow neurodegeneration in Alzheimer's and Parkinson's diseases. It was postulated that certain carbamate esters would inhibit AChE and BChE with the concomitant release in the brain of...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.107.033928

    authors： Groner E,Ashani Y,Schorer-Apelbaum D,Sterling J,Herzig Y,Weinstock M

    更新日期：2007-06-01 00:00:00

  • The aryl hydrocarbon receptor interacts with transcription factor IIB.

    abstract：:The aryl hydrocarbon receptor (AHR) and its DNA binding partner, the AHR nuclear translocator (ARNT), are basic helix-loop-helix transcription factors that mediate many of the toxic and carcinogenic effects of polyhalogenated aromatic hydrocarbons. The basic regions of the AHR and ARNT contact the GCGTG recognition si...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Swanson HI,Yang JH

    更新日期：1998-10-01 00:00:00

  • Demonstration of both A1 and A2 adenosine receptors in DDT1 MF-2 smooth muscle cells.

    abstract：:Adenosine receptors of the A1 and A2 subtypes were characterized in membranes from DDT1 MF-2 smooth muscle cells. These cells possess a high density of A1 adenosine receptors (Bmax = 0.8-0.9 pmol/mg of protein), as measured by both agonist and antagonist radioligands. Agonists compete for [125I]N6-[2-(4-amino-3-iodoph...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Ramkumar V,Barrington WW,Jacobson KA,Stiles GL

    更新日期：1990-02-01 00:00:00

  • Structural requirements of analogues of polyamines for migration and growth of IEC-6 cells.

    abstract：:Healing of gastrointestinal mucosal lesions occurs through two processes: an early one involving cell migration and a later one in which cell division replaces lost cells. Both processes require the presence of polyamines, but the mechanism of action of these compounds is unknown. In the present study, we examined the...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： McCormack SA,Zimmerman BJ,Israel M,Blanner P,Johnson LR

    更新日期：1995-10-01 00:00:00

  • Comparison of alpha 1-adrenergic receptor subtypes distinguished by chlorethylclonidine and WB 4101.

    abstract：:We showed previously that subtypes of alpha 1-adrenergic receptors can be differentiated by selective inactivation with chlorethylclonidine (CEC) [Mol. Pharmacol. 32:505-510 (1987)] or by their affinities for the competitive antagonist WB 4101 [Nature (Lond.) 329:333-335 (1987)]. Examining eight rat tissues, the propo...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Minneman KP,Han C,Abel PW

    更新日期：1988-05-01 00:00:00

  • Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643).

    abstract：:The cardiac action potential is generated by a concerted action of different ion channels and transporters. Dysfunction of any of these membrane proteins can give rise to cardiac arrhythmias, which is particularly true for the repolarizing potassium channels. We suggest that an increased repolarization current could b...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.105.015859

    authors： Hansen RS,Diness TG,Christ T,Demnitz J,Ravens U,Olesen SP,Grunnet M

    更新日期：2006-01-01 00:00:00

  • Antagonist conformations with the beta(2)-adrenergic receptor ligand binding pocket.

    abstract：:The interactions between beta-adrenergic receptor (beta AR) antagonists and the beta(2)AR were studied with the use of photoaffinity labels. A proteolytic map of the receptor was made and confirmed through amino-terminal amino acid sequencing by locating sites of derivatization. [125I]Iodoazidothiophenylalprenolol (IA...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Hockerman GH,Girvin ME,Malbon CC,Ruoho AE

    更新日期：1996-06-01 00:00:00

  • Identification of four novel exon 5 splice variants of the mouse mu-opioid receptor gene: functional consequences of C-terminal splicing.

    abstract：:The rat mu-opioid receptor clone in which novel exon 5 was found in the place of exon 4 (MOR-1B) was one of the first MOR-1 variants described. We now have identified the mouse homolog of the rat MOR-1B as well as four additional variants derived from splicing from exon 3 into different sites within exon 5. The sequen...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.105.011858

    authors： Pan YX,Xu J,Bolan E,Moskowitz HS,Xu M,Pasternak GW

    更新日期：2005-09-01 00:00:00

  • Determination of structural domains for G protein coupling and ligand binding in beta 3-adrenergic receptor.

    abstract：:The beta 3-adrenergic receptor (beta 3AR) is a member of the super-family of G protein-coupled receptors that are characterized by seven putative transmembrane helices connected by hydrophilic loops. The mechanism by which the activated beta ARs transmit the signals across the plasma membrane involves the stimulation ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Guan XM,Amend A,Strader CD

    更新日期：1995-09-01 00:00:00

  • Differential regulation of peptide alpha-amidation by dexamethasone and disulfiram.

    abstract：:alpha-Amidation is essential for the function of many peptides in intercellular communication. This C-terminal modification is mediated in a two-step process by the hydroxylase and lyase activities of the bifunctional enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). The first step, catalyzed by peptidylgly...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.55.6.1067

    authors： Driscoll WJ,Mueller SA,Eipper BA,Mueller GP

    更新日期：1999-06-01 00:00:00

  • Potent inhibition of aldehyde dehydrogenase-2 by diphenyleneiodonium: focus on nitroglycerin bioactivation.

    abstract：:Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN) to yield nitric oxide (NO) or a related species that activates soluble guanylate cyclase (sGC), resulting in cGMP-mediated vasodilation. Accordingly, established ALDH2 inhibitors attenuate GTN-induced vasorela...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.113.086835

    authors： Neubauer R,Neubauer A,Wölkart G,Schwarzenegger C,Lang B,Schmidt K,Russwurm M,Koesling D,Gorren AC,Schrammel A,Mayer B

    更新日期：2013-09-01 00:00:00

  • Conformational dynamics of Kir3.1/Kir3.2 channel activation via δ-opioid receptors.

    abstract：:This study assessed how conformational information encoded by ligand binding to δ-opioid receptors (DORs) is transmitted to Kir3.1/Kir3.2 channels. Human embryonic kidney 293 cells were transfected with bioluminescence resonance energy transfer (BRET) donor/acceptor pairs that allowed us to evaluate independently reci...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.112.081950

    authors： Richard-Lalonde M,Nagi K,Audet N,Sleno R,Amraei M,Hogue M,Balboni G,Schiller PW,Bouvier M,Hébert TE,Pineyro G

    更新日期：2013-02-01 00:00:00

  • Stabilizers of the Max homodimer identified in virtual ligand screening inhibit Myc function.

    abstract：:Many human cancers show constitutive or amplified expression of the transcriptional regulator and oncoprotein Myc, making Myc a potential target for therapeutic intervention. Here we report the down-regulation of Myc activity by reducing the availability of Max, the essential dimerization partner of Myc. Max is expres...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.109.054858

    authors： Jiang H,Bower KE,Beuscher AE 4th,Zhou B,Bobkov AA,Olson AJ,Vogt PK

    更新日期：2009-09-01 00:00:00