Modelling and molecular dynamics of the interaction between the E3 ubiquitin ligase Itch and the E2 UbcH7.


:Itch, a member of the E6AP carboxy terminus (HECT) domain-containing family of ubiquitin E3 ligases, acts in concert with the ubiquitin activating enzyme (E1) and the ubiquitin conjugating enzyme (E2) to catalyze ubiquitylation of protein targets. This sub-family of E3s shares a 350 residue C-terminal HECT domain having a strictly conserved catalytic Cys, and recruiting its cognate ubiquitin-loaded E2. HECT domains possess intrinsic enzymatic activity, by accepting ubiquitin from an E2, forming a ubiquitin thiolester intermediate, and directly catalyzing ubiquitylation of the target protein. Several hypotheses have been proposed for the biochemical mechanism underlying the structural relationship of the HECT-E2 association and subsequent ubiquitin transfer. Nonetheless, a detailed characterization of the process is still missing. In this work, we have used molecular dynamic simulations, free energy calculations, protein modelling techniques and normal modes analysis to get a deeper characterization of the static and dynamical properties of this interaction mechanism. We hypothesize a correlated slow-frequency motion that involves two different hinge regions of the HECT domain. The identification of the amino acid residues responsible for the HECT-E2 interaction, and for the dynamical properties of the ubiquitin transfer process, may be of relevant interest for pharmacological and therapeutical purposes.


Biochem Pharmacol


Biochemical pharmacology


Raimondo D,Giorgetti A,Bernassola F,Melino G,Tramontano A




Has Abstract


2008-12-01 00:00:00














  • Alteration of spinal protein kinase C expression and kinetics in morphine, but not clonidine, tolerance.

    abstract::Antinociceptive synergism between spinally administered morphine and clonidine decreases to an additive interaction in morphine- and clonidine-tolerant mice. Spinally administered protein kinase C (PKC) inhibitors also decrease the synergism to addition. To determine whether chronic morphine or clonidine treatment alt...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Li Y,Roerig SC

    更新日期:1999-08-01 00:00:00

  • Inhibition of tumour-induced lipolysis in vitro and cachexia and tumour growth in vivo by eicosapentaenoic acid.

    abstract::Stimulation of lipolysis in murine adipocytes in response to a lipid-mobilizing factor produced by a cachexia-inducing murine adenocarcinoma was inhibited by eicosapentaenoic acid (EPA) with a Ki value of 104 microM. The inhibitory effect was strictly structurally specific, since other related fatty acids of both the ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Tisdale MJ,Beck SA

    更新日期:1991-01-01 00:00:00

  • The effect of unsaturated fatty acids on sodium nitroprusside stimulation of guanylate cyclase in the human astrocytoma clone, D384, and the human neuroblastoma clone, NB1-G.

    abstract::Sodium nitroprusside (SNP) stimulates cGMP formation to a greater extent in 20,000 g supernatant fractions of the human neuroblastoma clones NB1-G and SH-SY5Y than in the human astrocytoma clone D384. This suggests that these cell lines contain the soluble form of guanylate cyclase. Arachidonic, 8,11,14- and 11,14,17-...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Vaughan PF,Ball SG

    更新日期:1990-02-01 00:00:00

  • The prodigiosins, proapoptotic drugs with anticancer properties.

    abstract::The family of natural red pigments, called prodigiosins (PGs), characterised by a common pyrrolylpyrromethene skeleton, are produced by various bacteria. Some members have immunosuppressive properties and apoptotic effects in vitro and they have also displayed antitumour activity in vivo. Understanding the mechanism o...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Pérez-Tomás R,Montaner B,Llagostera E,Soto-Cerrato V

    更新日期:2003-10-15 00:00:00

  • Inverse gene expression patterns for macrophage activating hepatotoxicants and peroxisome proliferators in rat liver.

    abstract::Macrophage activation contributes to adverse effects produced by a number of hepatotoxic compounds. Transcriptional profiles elicited by two macrophage activators, LPS and zymosan A, were compared to those produced by 100 paradigm compounds (mostly hepatotoxicants) using cDNA microarrays. Several hepatotoxicants previ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: McMillian M,Nie AY,Parker JB,Leone A,Kemmerer M,Bryant S,Herlich J,Yieh L,Bittner A,Liu X,Wan J,Johnson MD

    更新日期:2004-06-01 00:00:00

  • Desensitization of neurotensin-induced phosphoinositide hydrolysis in transfected CHO cells.

    abstract::The regulation of neurotensin-induced phosphoinositide turnover was studied in transfected CHO cells expressing the rat neurotensin receptor. Stimulation of these cells with neurotensin resulted in an important, but transient, increase in inositol phosphate cell content. Preincubation of the cells with neurotensin dra...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Hermans E,Maloteaux JM

    更新日期:1996-06-28 00:00:00

  • Effect of acute and chronic intermittent hypoxia on DNA topoisomerase II alpha expression and mitomycin C-induced DNA damage and cytotoxicity in human colon cancer cells.

    abstract::Recently, we reported that alterations in topoisomerase II (topo II) activity appear to contribute to mitomycin C (MMC) resistance in HT-29R13 human colon cancer cells under aerobic conditions. In this study, the expression of topo II alpha and topo II beta in parent HT-29 and MMC resistant variant HT-29R13 cells was ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kang Y,Greaves B,Perry RR

    更新日期:1996-08-23 00:00:00

  • Selective modifications in the de novo biosynthesis of retinal phospholipids and glycerides by propranolol or phentolamine.

    abstract::The effects of propranolol or phentolamine on the metabolism of phospholipids, diacylglycerol, and triacylglycerol were studied in the bovine retina in vitro. Lipid labeling was followed during short-term incubation of intact bovine retinas with [U-14C]glycerol and [1-14C]palmitic acid. Each of these precursors was re...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: de Boschero MG,Bazan NG

    更新日期:1982-03-15 00:00:00

  • Thrombospondin 2 promotes tumor metastasis by inducing matrix metalloproteinase-13 production in lung cancer cells.

    abstract::Thrombospondin (TSP)-2, a matricellular glycoprotein of the TSP family, regulates multiple biological functions, including proliferation, angiogenesis, cell adhesion, and extracellular matrix (ECM) modeling. The clinical relevance of TSP-2 has been explored in many different cancers. TSP-2 expression levels vary betwe...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Liu JF,Lee CW,Tsai MH,Tang CH,Chen PC,Lin LW,Lin CY,Lu CH,Lin YF,Yang SH,Chao CC

    更新日期:2018-09-01 00:00:00

  • Immunocytochemical localization of cytochrome P-450 in hepatic and extra-hepatic tissues of the rat with a monoclonal antibody against cytochrome P-450 c.

    abstract::The cellular distribution of cytochrome P-450 has been studied in the liver and a number of extrahepatic tissues in the rat by immunocytochemistry, using an antibody raised against cytochrome P-450 form c. Immunoreactive cytochrome P-450, most probably form c, was found in the proximal tubules of the kidney, in the Cl...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Foster JR,Elcombe CR,Boobis AR,Davies DS,Sesardic D,McQuade J,Robson RT,Hayward C,Lock EA

    更新日期:1986-12-15 00:00:00

  • Specific binding and uptake of extracellular nicotinamide in human leukemic K-562 cells.

    abstract::Extracellular nicotinamide is well recognized as the primary precursor to the cellular synthesis of NAD. NAD is a pivotal molecule in regulating the energy and redox potentials of cells via synthesis of ATP and NAD(P)/NAD(P)H ratios. NAD turnover in cells is very rapid due to NAD catabolism via ADP-ribosylation reacti...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Olsson A,Olofsson T,Pero RW

    更新日期:1993-03-24 00:00:00

  • Epithelial peptide antibiotics.

    abstract::Surfaces of higher eukaryotes such as plants, invertebrates, and vertebrates, including humans, are normally covered with microorganisms but usually are not infected by them. The reason, apart from physical barriers, is the production of gene-encoded antimicrobial peptides by epithelial cells. Many novel antimicrobial...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Schröder JM

    更新日期:1999-01-15 00:00:00

  • Hydralazine inhibition of the post-translational hydroxylation of deoxyhypusine, a polyamine-derived amino acid.

    abstract::Logarithmically growing Chinese hamster ovary cells, cultured in the presence of [1,4-14C]putrescine, synthesize a protein(s) containing the unusual amino acid hypusine [N epsilon-(4-amino-2-hydroxybutyl)lysine]. This protein was separated and identified by two-dimensional gel electrophoresis and fluorography. The lab...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Paz MA,Torrelio BM,Gallop PM

    更新日期:1984-03-01 00:00:00

  • On the binding of a 3-alpha-methylated digitoxigenin-glucoside to ouabain receptors in heart muscle homogenate.

    abstract::3-alpha-Methyl substituted digitoxigenin-3-beta-glucoside (methyl-dtg-gluc) displays unusual features, e.g. a high dissociation rate constant from its binding site leading to rapid reversibility of the inotropic and toxic effects, and a flat dose-response curve attaining higher inotropic maxima thus indicating an incr...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lüllmann H,Mohr K

    更新日期:1982-08-01 00:00:00

  • The metabolism of the xenobiotic triacylglycerols, rac-1- and sn-2- (3-phenoxybenzoyl)-dipalmitoylglycerol, following intravenous administration to the rat.

    abstract::The metabolism of 3-phenoxybenzoic acid (3PBA) in the form of triacylglycerol conjugates was compared with that of non-esterified 3PBA. Three radiolabeled triacylglycerols (rac-1-(3-phenoxy-[ring-14C]-benzoyl)-2,3-dipalmitoylglycerol (1(3PBA)DPG), sn-2-(3-phenoxy-[ring-14C]benzoyl)-1,3-dipalmitoylglycerol (2(3PBA)DPG)...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Haselden JN,Dodds PF,Hutson DH

    更新日期:1998-12-15 00:00:00

  • Effects of purified green and black tea polyphenols on cyclooxygenase- and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosa and colon tumor tissues.

    abstract::The effects of green and black tea polyphenols on cyclooxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonic acid metabolism in normal human colon mucosa and colon cancers were investigated. At a concentration of 30 microg/mL, (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatech...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Hong J,Smith TJ,Ho CT,August DA,Yang CS

    更新日期:2001-11-01 00:00:00

  • Effect of O6-benzylguanine on the sensitivity of human colon tumor xenografts to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU).

    abstract::A number of trials were conducted to determine the effect of O6-benzylguanine pretreatment on the sensitivity of human colon tumor xenografts to the antitumor effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). O6-Benzylguanine has been shown to inactivate the DNA repair protein, O6-alkylguanine-DNA alkyltransfera...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dolan ME,Pegg AE,Moschel RC,Grindey GB

    更新日期:1993-07-20 00:00:00

  • Induction by staurosporine of hepatocyte growth factor production in human skin fibroblasts independent of protein kinase inhibition.

    abstract::Staurosporine is one of the most potent and well known inhibitors of protein kinases, and it is often used to study the involvement of protein kinases in signal transduction pathways. We now report that staurosporine can induce the production of hepatocyte growth factor (HGF) independently of protein kinase inhibition...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Yagi Y,Sotani T,Nagao T,Horio T,Yamamoto I,Gohda E

    更新日期:2003-11-01 00:00:00

  • Identification of novel transplantable GPCR recycling motif for drug discovery.

    abstract::β1-Adrenergic receptor (β1-AR) agonists and antagonists are widely used in the treatment of major cardiovascular diseases such as heart failure and hypertension. The β1-AR like other G protein-coupled receptors (GPCRs) are endocytosed in response to intense agonist activation. Recycling of the agonist-internalized β1-...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Nooh MM,Mancarella S,Bahouth SW

    更新日期:2016-11-15 00:00:00

  • Evidence for the lack of hepatic N-acetyltransferase in suncus (Suncus murinus).

    abstract::The abilities of liver cytosol fractions from the suncus and Sprague-Dawley (SD) rats to N-acetylate aniline, p-aminobenzoic acid, p-aminosalicylic acid and 2-aminofluorene (AF) were compared. The cytosol from rats N-acetylated these substrates at efficient rates, whereas the cytosol from the suncus did not N-acetylat...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Nakura H,Itoh S,Kusano H,Ishizone H,Deguchi T,Kamataki T

    更新日期:1995-10-12 00:00:00

  • Identification and selective inhibition of four distinct soluble forms of cyclic nucleotide phosphodiesterase activity from kidney.

    abstract::Homogenization of rat kidney under isotonic conditions and in the presence of protease inhibitors showed that some 92% of the cyclic AMP phosphodiesterase activity and some 83% of the cyclic GMP phosphodiesterase activity was released into the soluble fraction. Analysis of soluble phosphodiesterase activity by FPLC on...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Hoey M,Houslay MD

    更新日期:1990-07-15 00:00:00

  • Carbazolequinone induction of caspase-dependent cell death in Src-overexpressing cells.

    abstract::We previously reported that RSV-transformed quail neuroretina cells (QNR-ts68) were highly resistant to apoptosis provoked by serum withdrawal, and that this property was due to v-Src kinase activity. The present study investigates the cytotoxic effect and the functional mechanism of carbazolequinone-mediated cell dea...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Aouacheria A,Néel B,Bouaziz Z,Dominique R,Walchshofer N,Paris J,Fillion H,Gillet G

    更新日期:2002-12-01 00:00:00

  • Cytotoxicity of dichloromethane diphosphonate and of 1-hydroxyethane-1,1-diphosphonate in the amoebae of the slime mould Dictyostelium discoideum. A 31P NMR study.

    abstract::Two pyrophosphate analogues, dichloromethane diphosphonate (Cl2MDP), and 1-hydroxyethane-1,1-diphosphonate (EHDP), at concentrations of 0.5-1 mM, efficiently inhibited the growth of amoebae of the slime mould Dictyostelium discoideum. Cell viability decreased markedly upon incubation with the diphosphonates. The mecha...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Pelorgeas S,Martin JB,Satre M

    更新日期:1992-12-01 00:00:00

  • Evidence in vivo for elevation of intracellular free Ca2+ in the liver after diquat, acetaminophen, and CCl4.

    abstract::Several hepatotoxic agents with varied chemical mechanisms of toxicity (acetaminophen, diquat, and CCl4) depress membrane calcium pumps and/or enhance the permeability of membranes to calcium. To probe the relevance of these findings to maintenance of calcium homeostasis after toxins in vivo, we measured the activity ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Tsokos-Kuhn JO

    更新日期:1989-09-15 00:00:00

  • Interactions of 5-hydroxytryptamine with oxidative enzymes.

    abstract::Peroxidase (EC, ceruloplasmin (human type X)/O2, and tyrosinase (EC all oxidized the indolic neurotransmitter 5-hydroxytryptamine (5-HT) in the physiological pH domain. Peroxidase/H2O2 oxidized 5-HT at pH values down to about 2.5. All oxidation reactions generated complex mixtures of produ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wrona MZ,Dryhurst G

    更新日期:1991-04-15 00:00:00

  • In vivo metabolism of alpha,alpha,beta,beta-tetradeutero-N, N-dimethyltryptamine in rodent brain.

    abstract::The metabolism of alpha,alpha,beta,beta- tetradeutero -N,N -dimethyltryptamine ( D4DMT ) in rat brain in vivo as a function of time and dose was examined. Quantification of D4DMT and its respective deutero-metabolites was accomplished using gas chromatographic/mass spectrometric/selected ion monitoring/isotope dilutio...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Barker SA,Beaton JM,Christian ST,Monti JA,Morris PE

    更新日期:1984-05-01 00:00:00

  • Effects of cell isolation procedures and radioligand selection on the characterization of human leukocyte beta-adrenergic receptors.

    abstract::Radioligand binding techniques are commonly used in the characterization of beta-adrenergic receptors on human peripheral leukocytes. Accurate interpretation of receptor binding parameters necessitates appropriate radioligand selection. In addition, cell isolation techniques should have minimal effect on the binding p...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Szefler SJ,Edwards CK 3rd,Haslett C,Zahniser NR,Miller JA,Henson PM

    更新日期:1987-05-15 00:00:00

  • Structural requirements of Dictyostelium differentiation-inducing factors for their stalk-cell-inducing activity in Dictyostelium cells and anti-proliferative activity in K562 human leukemic cells.

    abstract::The differentiation-inducing factor-1 (DIF-1) is a lipophilic signal molecule (chlorinated alkylphenone) that induces stalk-cell differentiation in the cellular slime mould Dictyostelium discoideum. It has also been shown that DIF-1 and its derivative (DIF-3) suppress cell growth in mammalian tumor cells. In the prese...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Gokan N,Kikuchi H,Nakamura K,Oshima Y,Hosaka K,Kubohara Y

    更新日期:2005-09-01 00:00:00

  • Activation of misonidazole by rat liver microsomes and purified NADPH-cytochrome c reductase.

    abstract::Rat liver microsomes and purified NADPH-cytochrome c reductase metabolized [14C]misonidazole anaerobically to a reactive intermediate that covalently binds to tissue macromolecules. Air strongly inhibited the binding whereas carbon monoxide had no effect, indicating that misonidazole is activated via reduction and not...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: McManus ME,Lang MA,Stuart K,Strong J

    更新日期:1982-02-15 00:00:00

  • Pioglitazone, a PPARγ agonist, attenuates PDGF-induced vascular smooth muscle cell proliferation through AMPK-dependent and AMPK-independent inhibition of mTOR/p70S6K and ERK signaling.

    abstract::Pioglitazone (PIO), a PPARγ agonist that improves glycemic control in type 2 diabetes through its insulin-sensitizing action, has been shown to exhibit beneficial effects in the vessel wall. For instance, it inhibits vascular smooth muscle cell (VSMC) proliferation, a major event in atherosclerosis and restenosis afte...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Osman I,Segar L

    更新日期:2016-02-01 00:00:00