Detailed structural characterization of unbound protein phosphatase 1 inhibitors.


:Protein phosphatase 1 (PP1) is an essential and ubiquitous serine/threonine protein phosphatase that is regulated by more than 100 known inhibitor and targeting proteins. It is currently unclear how protein inhibitors distinctly and specifically regulate PP1 to enable rapid responses to cellular alterations. We demonstrate that two PP1 inhibitors, I-2 and DARPP-32, belong to the class of intrinsically unstructured proteins (IUPs). We show that both inhibitors have distinct preferences for transient local and long-range structure. These preferences are likely their structural signature for their interaction with PP1. Furthermore, we show that upon phosphorylation of Thr(34) in DARPP-32, which turns DARPP-32 into a potent inhibitor of PP1, neither local nor long-range structure of DARPP-32 is altered. Therefore, our data suggest a role for these transient three-dimensional topologies in binding mechanisms that enable extensive contacts with PP1's invariant surfaces. Together, these interactions enable potent and selective inhibition of PP1.






Dancheck B,Nairn AC,Peti W




Has Abstract


2008-11-25 00:00:00












  • Primary Deuterium Kinetic Isotope Effects: A Probe for the Origin of the Rate Acceleration for Hydride Transfer Catalyzed by Glycerol-3-Phosphate Dehydrogenase.

    abstract::Large primary deuterium kinetic isotope effects (1° DKIEs) on enzyme-catalyzed hydride transfer may be observed when the transferred hydride tunnels through the energy barrier. The following 1° DKIEs on kcat/ Km and relative reaction driving force are reported for wild-type and mutant glycerol-3-phosphate dehydrogenas...


    pub_type: 杂志文章


    authors: Reyes AC,Amyes TL,Richard JP

    更新日期:2018-07-24 00:00:00

  • Critical micelle concentrations of gangliosides.

    abstract::The micellar properties of mixed, bovine gangliosides and purified galactosyl-N-acetylacetylgalactosaminyl (N-acetylneuraminyl) galactosylglucosylceramide were studied by gel filtration, equilibrium dialysis, and band and boundary centrifugation in sucrose gradients. The dissociation of micelles is very slow (days) in...


    pub_type: 杂志文章


    authors: Formisano S,Johnson ML,Lee G,Aloj SM,Edelhoch H

    更新日期:1979-03-20 00:00:00

  • Mechanistic studies of the oxygen-mediated oxidation of nitrosylhemoglobin.

    abstract::Nitrosylhemoglobin (HbFe(II)NO) has been shown to be generated in vivo from the reaction of deoxyHb with NO(*) as well as with nitrite. Despite the physiological importance attributed to this form of Hb, its reactivity has not been investigated in detail. In this study, we showed that the rate of oxidation of HbFe(II)...


    pub_type: 杂志文章


    authors: Herold S,Röck G

    更新日期:2005-04-26 00:00:00

  • Photochemical cleavage of DNA by nitrobenzamides linked to 9-aminoacridine.

    abstract::Nitrobenzamido ligands linked to the DNA intercalator 9-aminoacridine via poly(methylene) chains induce single-strand nicks in DNA upon irradiation with long-wavelength ultraviolet light (lambda greater than or equal to 300 nm). Optimal photocleavage activity was found for the reagent 9-[[6-(4-nitrobenzamido)hexyl]ami...


    pub_type: 杂志文章


    authors: Nielsen PE,Jeppesen C,Egholm M,Buchardt O

    更新日期:1988-08-23 00:00:00

  • Purification and partial characterization of rat liver folate binding protein: cytosol I.

    abstract::The high molecular weight folate binding protein of rat liver cytosol has been purified to apparent homogeneity. Purification was achieved by using a combination of gel filtration, O-(diethylaminoethyl)cellulose chromatography, and affinity chromatography. This folate binding protein was initially identified during pu...


    pub_type: 杂志文章


    authors: Cook RJ,Wagner C

    更新日期:1982-08-31 00:00:00

  • Reversible phosphorylation as a controlling factor for sustaining calcium oscillations in HeLa cells: Involvement of calmodulin-dependent kinase II and a calyculin A-inhibitable phosphatase.

    abstract::The role of reversible phosphorylation in histamine-induced Ca2+ oscillations in HeLa cells has been investigated by using various activators and inhibitors of protein kinases and phosphatases. Electroporation was employed to introduce impermeable materials into single cells, which proved to be a useful and convenient...


    pub_type: 杂志文章


    authors: Zhu DM,Tekle E,Chock PB,Huang CY

    更新日期:1996-06-04 00:00:00

  • Substrate specificity and kinetic characteristics of angiotensin converting enzyme.

    abstract::Furanacryloyl-Phe-Gly-Gly has been shown to be a convenient substrate for angiotensin converting enzyme (dipeptidyl carboxypeptidase, EC A detailed kinetic analysis of the hydrolysis of this substrate indicates normal Michaelis-Menten behavior with kcat = 19000 min-1 and KM = 3.0 x 10(-4) M determined at pH...


    pub_type: 杂志文章


    authors: Bünning P,Holmquist B,Riordan JF

    更新日期:1983-01-04 00:00:00

  • Enzymatic Synthesis of a Fluorogenic Reporter Substrate and the Development of a High-Throughput Assay for Fucosyltransferase VIII Provide a Toolkit to Probe and Inhibit Core Fucosylation.

    abstract::We report a straightforward enzymatic synthesis of the 4-methylumbelliferyl glycoside of a complex-type oligosaccharide substrate for core fucosylation. We demonstrate the use of this synthetic glycoconjugate in a newly developed enzyme assay to probe the activity and inhibition of fucosyltransferase VIII, which catal...


    pub_type: 杂志文章


    authors: Soroko M,Kwan DH

    更新日期:2020-06-09 00:00:00

  • Replacement of disulfides by amide bonds in the relaxin-like factor (RLF/INSL3) reveals a role for the A11-B10 link in transmembrane signaling.

    abstract::The relaxin-like factor (RLF) also named insulin-like 3 (INSL3) consists of two polypeptide chains linked by two interchain and one intrachain disulfide bond. RLF binds to its receptor (LGR8 also named RXFP2) through the B chain and initiates transmembrane communication by activating the adenylate cyclase through the ...


    pub_type: 杂志文章


    authors: Büllesbach EE,Schwabe C

    更新日期:2012-05-22 00:00:00

  • Role of Calcium in the thermal stability of thermolysin.

    abstract::The effect of calcium ion on the thermal stability of thermolysin has been investigated. The native protein undergoes an irreversible structural change and autolysis at high temperature. Analysis of the calcium ion dependence of the apparent melting temperature observed spectroscopically gives an apparent deltaH of -x...


    pub_type: 杂志文章


    authors: Dahlquist FW,Long JW,Bigbee WL

    更新日期:1976-03-09 00:00:00

  • Interaction of complement proteins C5b-6 and C5b-7 with phospholipid vesicles: effects of phospholipid structural features.

    abstract::Complement components C5b-6 and C7 assemble to form C5b-7, which then interacts with membranes and commits the membrane attack complex to a target site. This protein-membrane association event was investigated to determine possible structural features that could contribute to a selective membrane attack. This system m...


    pub_type: 杂志文章


    authors: Silversmith RE,Nelsestuen GL

    更新日期:1986-11-18 00:00:00

  • Mutagenesis of a conserved glutamate reveals the contribution of electrostatic energy to adenosylcobalamin co-C bond homolysis in ornithine 4,5-aminomutase and methylmalonyl-CoA mutase.

    abstract::Binding of substrate to ornithine 4,5-aminomutase (OAM) and methylmalonyl-CoA mutase (MCM) leads to the formation of an electrostatic interaction between a conserved glutamate side chain and the adenosyl ribose of the adenosylcobalamin (AdoCbl) cofactor. The contribution of this residue (Glu338 in OAM from Clostridium...


    pub_type: 杂志文章


    authors: Makins C,Pickering AV,Mariani C,Wolthers KR

    更新日期:2013-02-05 00:00:00

  • Specific photoaffinity labeling of Tyr-49 on the light chain in the steroid-combining site of a mouse monoclonal anti-estradiol antibody using two epimeric 6alpha- and 6beta-(5-azido-2-nitrobenzoyl)amidoestradiol photoreagents.

    abstract::A mouse monoclonal anti-7-(O-carboxymethyl)oximinoestradiol antibody was photoaffinity labeled with two cross-reactive 6alpha- and 6beta-(5-azido-2-nitrobenzoyl)amido[17alpha-3H]estradiol photoreagents (6alpha- and 6beta-ANBA-[17alpha-3H]estradiol). Covalently bound radioactivity was found exclusively on the light cha...


    pub_type: 杂志文章


    authors: Rousselot P,Mappus E,Blachère T,de Ravel MR,Grenot C,Tonnelle C,Cuilleron CY

    更新日期:1997-06-24 00:00:00

  • Estrogen-induced changes in high-energy phosphate metabolism in rat uterus: 31P NMR studies.

    abstract::Changes in the concentrations of high-energy phosphate metabolites were measured by 31P NMR spectroscopy of surviving rat uteri from 0-48 h following estrogen administration. Concentrations (millimoles per kilogram wet weight) of these metabolites in the untreated immature uterus, measured at 4 degrees C, were found t...


    pub_type: 杂志文章


    authors: Degani H,Shaer A,Victor TA,Kaye AM

    更新日期:1984-06-05 00:00:00

  • Structure of the third cytoplasmic loop of bovine rhodopsin.

    abstract::The three-dimensional high-resolution structure of rhodopsin is unknown, as is the case for almost all integral membrane patients. As part of an alternative approach to determine of membrane protein structure, we are pursuing the structure of cytoplasmic domains of this G-protein receptor. A peptide, rhoIII, with the ...


    pub_type: 杂志文章


    authors: Yeagle PL,Alderfer JL,Albert AD

    更新日期:1995-11-14 00:00:00

  • Three-dimensional structure of the apo form of the N-terminal EGF-like module of blood coagulation factor X as determined by NMR spectroscopy and simulated folding.

    abstract::The three-dimensional structure of a 42-residue fragment containing the N-terminal EGF-like module of blood coagulation factor X was determined by means of 2D NMR spectroscopy and computer simulation. The spectroscopic data consisted of 370 NOE distances and 27 dihedral angle constraints. These were used to generate p...


    pub_type: 杂志文章


    authors: Ullner M,Selander M,Persson E,Stenflo J,Drakenberg T,Teleman O

    更新日期:1992-07-07 00:00:00

  • Molecular characterization of the AP180 coated vesicle assembly protein.

    abstract::Recently, a new clathrin assembly protein (AP180) has been purified from coated vesicles of bovine brain (Ahle & Ungewickell, 1986). This protein has been shown to promote polymerization of clathrin into a homogeneous population of baskets under conditions where pure clathrin does not polymerize by itself. We have pur...


    pub_type: 杂志文章


    authors: Prasad K,Lippoldt RE

    更新日期:1988-08-09 00:00:00

  • NMR structures of loop B RNAs from the stem-loop IV domain of the enterovirus internal ribosome entry site: a single C to U substitution drastically changes the shape and flexibility of RNA.

    abstract::The 5'-untranslated region of positive-strand RNA viruses harbors many cis-acting RNA structural elements that are important for various viral processes such as replication, translation, and packaging of new virions. Among these is loop B RNA of the stem-loop IV domain within the internal ribosomal entry site (IRES) o...


    pub_type: 杂志文章


    authors: Du Z,Ulyanov NB,Yu J,Andino R,James TL

    更新日期:2004-05-18 00:00:00

  • The role of Gly-4 of human cystatin A (stefin A) in the binding of target proteinases. Characterization by kinetic and equilibrium methods of the interactions of cystatin A Gly-4 mutants with papain, cathepsin B, and cathepsin L.

    abstract::The importance of the evolutionarily conserved Gly-4 residue for the affinity and kinetics of interaction of cystatin A with several cysteine proteinases was assessed by site-directed mutagenesis. Even the smallest replacement, by Ala, resulted in approximately 1000-, approximately 10- and approximately 6000-fold decr...


    pub_type: 杂志文章


    authors: Estrada S,Nycander M,Hill NJ,Craven CJ,Waltho JP,Björk I

    更新日期:1998-05-19 00:00:00

  • Tyrosine kinase-mediated serine phosphorylation of adenylyl cyclase.

    abstract::Receptor tyrosine kinase (RTK) activation is associated with modulation of heptahelical receptor-stimulated adenylyl cyclase responses. The mechanisms underlying the RTK-mediated enhancement of adenylyl cyclase function remain unclear. In the present studies, we show that the tyrosine kinase-dependent enhancement of a...


    pub_type: 杂志文章


    authors: Tan CM,Kelvin DJ,Litchfield DW,Ferguson SS,Feldman RD

    更新日期:2001-02-13 00:00:00

  • Ligand-specific structural changes in the vitamin D receptor in solution.

    abstract::Vitamin D receptor (VDR) is a member of the nuclear hormone receptor superfamily. When bound to a variety of vitamin D analogues, VDR manifests a wide diversity of physiological actions. The molecular mechanism by which different vitamin D analogues cause specific responses is not understood. The published crystallogr...


    pub_type: 杂志文章


    authors: Singarapu KK,Zhu J,Tonelli M,Rao H,Assadi-Porter FM,Westler WM,DeLuca HF,Markley JL

    更新日期:2011-12-27 00:00:00

  • N-linked neutral sugar chains of aminopeptidase N purified from rat small intestinal brush-border membrane.

    abstract::Neutral oligosaccharides, which accounted for 74% of the total N-linked sugar chains released by hydrazinolysis of rat small intestinal aminopeptidase N, were investigated on a structural basis. They are mainly composed of complex-type sugar chains with tri- and tetraantennary structures, and small amounts of high man...


    pub_type: 杂志文章


    authors: Takasaki S,Erickson RH,Kim YS,Kochibe N,Kobata A

    更新日期:1991-09-17 00:00:00

  • Nonsequential unfolding of the alpha/beta barrel protein indole-3-glycerol-phosphate synthase.

    abstract::The folding of the enzyme indole-3-glycerol-phosphate synthase (IGPS), a member of the (alpha/beta)8 fold family, has been studied. At least two folding intermediates have been detected using spectroscopic and activity measurements in combination with gel filtration chromatography. These two intermediates are produced...


    pub_type: 杂志文章


    authors: Sánchez del Pino MM,Fersht AR

    更新日期:1997-05-06 00:00:00

  • Three-dimensional structure of N5-carboxyaminoimidazole ribonucleotide synthetase: a member of the ATP grasp protein superfamily.

    abstract::Escherichia coli PurK, a dimeric N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) synthetase, catalyzes the conversion of 5-aminoimidazole ribonucleotide (AIR), ATP, and bicarbonate to N5-CAIR, ADP, and Pi. Crystallization of both a sulfate-liganded and the MgADP-liganded E. coli PurK has resulted in structures at 2....


    pub_type: 杂志文章


    authors: Thoden JB,Kappock TJ,Stubbe J,Holden HM

    更新日期:1999-11-23 00:00:00

  • Ionization equilibria for side-chain carboxyl groups in oxidized and reduced human thioredoxin and in the complex with its target peptide from the transcription factor NF kappa B.

    abstract::The pH dependence of the 13C chemical shifts of the side-chain carboxyl carbons of all Asp and Glu residues in the reduced and oxidized states of human thioredoxin and in a mixed disulfide complex of human thioredoxin with a target peptide from the transcription factor NF kappa B has been investigated by multidimensio...


    pub_type: 杂志文章


    authors: Qin J,Clore GM,Gronenborn AM

    更新日期:1996-01-09 00:00:00

  • Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202-->alanine carbonic anhydrase II variant.

    abstract::The crystal structure of a human carbonic anhydrase II (CAII) variant, cis-proline-202-->alanine (P202A), has been determined at 1.7-A resolution, indicating that the wild-type geometry, including the cis-peptidyl linkage, is retained upon substitution of proline by alanine. The CO2 hydrase activity and affinity for s...


    pub_type: 杂志文章


    authors: Tweedy NB,Nair SK,Paterno SA,Fierke CA,Christianson DW

    更新日期:1993-10-19 00:00:00

  • Structure of FAD-bound L-aspartate oxidase: insight into substrate specificity and catalysis.

    abstract::L-Aspartate oxidase (Laspo) catalyzes the conversion of L-Asp to iminoaspartate, the first step in the de novo biosynthesis of NAD(+). This bacterial pathway represents a potential drug target since it is absent in mammals. The Laspo R386L mutant was crystallized in the FAD-bound catalytically competent form and its t...


    pub_type: 杂志文章


    authors: Bossi RT,Negri A,Tedeschi G,Mattevi A

    更新日期:2002-03-05 00:00:00

  • Functional interactions in cytochrome P450BM3. Evidence that NADP(H) binding controls redox potentials of the flavin cofactors.

    abstract::NADP(H) binding is essential for fast electron transfer through the flavoprotein domain of the fusion protein P450BM3. Here we characterize the interaction of NADP(H) with the oxidized and partially reduced enzyme and the effect of this interaction on the redox properties of flavin cofactors and electron transfer. Mea...


    pub_type: 杂志文章


    authors: Murataliev MB,Feyereisen R

    更新日期:2000-10-17 00:00:00

  • Solid state 15N NMR evidence for a complex Schiff base counterion in the visual G-protein-coupled receptor rhodopsin.

    abstract::Using the baculovirus/Sf9 cell expression system, we have incorporated 99% 15N-enriched [alpha,epsilon-15N2]-L-lysine into the rod visual pigment rhodopsin. We have subsequently investigated the protonated Schiff base (pSB) linkage in the [alpha, epsilon-15N2]Lys-rhodopsin with cross-polarization magic angle spinning ...


    pub_type: 杂志文章


    authors: Creemers AF,Klaassen CH,Bovee-Geurts PH,Kelle R,Kragl U,Raap J,de Grip WJ,Lugtenburg J,de Groot HJ

    更新日期:1999-06-01 00:00:00

  • Isotope-edited Fourier transform infrared spectroscopy studies of calmodulin's interaction with its target peptides.

    abstract::The ubiquitous calcium-binding protein calmodulin (CaM) regulates a wide variety of cellular events by binding to and activating many distinct target enzymes. The CaM-binding domains of most of these enzymes are contained in a contiguous stretch of amino acids with a length of approximately 20 residues. In this work, ...


    pub_type: 杂志文章


    authors: Zhang M,Fabian H,Mantsch HH,Vogel HJ

    更新日期:1994-09-13 00:00:00