Homo- and hetero-dimerization of human UDP-glucuronosyltransferase 2B7 (UGT2B7) wild type and its allelic variants affect zidovudine glucuronidation activity.


:Most human UDP-glucuronosyltransferase (UGT; EC genes contain non-synonymous single nucleotide polymorphisms (nsSNPs) which cause amino acid substitutions. Allelic variants caused by nsSNPs may exhibit absent or reduced enzyme activity. UGT2B7 is one of the most important UGTs that glucuronidates abundant endobiotics and xenobiotics, such as estriol, morphine, and anticancer drugs. Three nsSNPs, UGT2B7*71S (211G>T), UGT2B7*2 (802C>T) and UGT2B7*5 (1192G>A) are observed in the UGT2B7 gene, and they code for allozymes UGT2B7*71S (A71S), UGT2B7*2 (H268Y), and UGT2B7*5 (D398N). UGT2B7 has been observed to form oligomers that affect its enzymatic activity and in this study, we investigated protein-protein interactions among UGT2B7 allozymes wild type (WT), A71S, H268Y and D398N, by performing a systematic quantitative fluorescence resonance energy transfer (FRET) analysis in combination with co-immunoprecipitation assay. Quantitative FRET analysis revealed that UGT2B7 allozymes formed homo- and hetero-dimers and showed distinct features in donor-acceptor distances. Both codon 71 and codon 268 in the N-terminal domain were involved in the dimeric interaction. Co-immunoprecipitation experiments also proved that UGT2B7 allozymes formed stable dimers. The glucuronidation activities of homo- and hetero-dimers were further tested with zidovudine as the substrate. An increase in activity was observed when WT hetero-dimerized with A71S compared with homo-dimers, while both H268Y and D398N impaired the activity of WT and A71S by forming hetero-dimers. In addition, zidovudine glucuronidation activity is associated with FRET distance. These findings provide insights into the consequences of amino acid substitution in UGT2B7 on zidovudine glucuronidation and the association between protein-protein interaction and glucuronidation activity.


Biochem Pharmacol


Biochemical pharmacology


Yuan L,Qian S,Xiao Y,Sun H,Zeng S




Has Abstract


2015-05-01 00:00:00














  • Relationship between NAD(P)H:quinone oxidoreductase 1 (NQO1) levels in a series of stably transfected cell lines and susceptibility to antitumor quinones.

    abstract::To investigate the importance of NAD(P)H:quinone oxidoreductase 1 (or DT-diaphorase; NQO1) in the bioactivation of antitumor quinones, we established a series of stably transfected cell lines derived from BE human colon adenocarcinoma cells. BE cells have no NQO1 activity due to a genetic polymorphism. The new cell li...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Winski SL,Swann E,Hargreaves RH,Dehn DL,Butler J,Moody CJ,Ross D

    更新日期:2001-06-15 00:00:00

  • Inhibition by the protein kinase inhibitor HA1077 of the activation of NADPH oxidase in human neutrophils.

    abstract::The effect of an inhibitor of protein kinase, HA1077 [1-(5-isoquinolinesulfonyl)-homopiperazine HCl], and its hydroxylated metabolite, HA1100, on the activation of NADPH oxidase in human neutrophils were studied. Cells were preincubated with each drug for 10 min and then activated by treatment with phorbol myristate a...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Arai M,Sasaki Y,Nozawa R

    更新日期:1993-10-19 00:00:00

  • Attenuation by glutathione of hsp72 gene expression induced by cadmium in cisplatin-resistant human ovarian cancer cells.

    abstract::Intracellular GSH has some effects on protecting cells against cadmium and is involved in the development of resistance to cisplatin (CDDP). To determine the effects of intracellular GSH on expression of the heat shock genes (hsp) induced by cadmium in CDDP-resistant cancer cells, we used two human ovarian cancer cell...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Abe T,Gotoh S,Higashi K

    更新日期:1999-07-01 00:00:00

  • The angiogenic process as a therapeutic target in cancer.

    abstract::Angiogenesis has emerged as a critical process for tumour progression. Identifying key pathways involved in the regulation and promotion of angiogenesis has resulted in the development of numerous approaches targeting pro-angiogenic signalling pathways. The most prominent and characterised pro-angiogenic pathway is th...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Bridges EM,Harris AL

    更新日期:2011-05-15 00:00:00

  • Hepatic alcohol metabolizing enzymes after prolonged administration of sex hormones and alcohol in female rats.

    abstract::To study the effect of sex hormones and alcohol on the hepatic activities of alcohol metabolizing enzymes, estradiol or testosterone were administered for 4 weeks to ovarectomized or sham operated adult female rats pair-fed nutritionally adequate liquid diets containing either alcohol (36% of total calories) or isocal...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Teschke R,Wannagat FJ,Löwendorf F,Strohmeyer G

    更新日期:1986-02-01 00:00:00

  • Inhibition of human red blood cell glutathione reductase by valproic acid.

    abstract::Glutathione reductase (GR) one of the enzymes of the glutathione redox cycle, plays a salient role in maintaining appropriate cellular levels of reduced glutathione. The enzyme in human red blood cells is inhibited in vitro by the anticonvulsant drug valproic acid (VPA). The inhibition is dose-dependent, reversible, u...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Cotariu D,Evans S,Lahat E,Theitler J,Bistritzer T,Zaidman JL

    更新日期:1992-02-04 00:00:00

  • Characterization of AN6001, a positive allosteric modulator of α6β2-containing nicotinic acetylcholine receptors.

    abstract::α6β2-Containing nicotinic acetylcholine receptors (α6β2* nAChRs) are predominantly expressed in midbrain dopaminergic neurons, including substantia nigra pars compacta (SNc) neurons and their projections to striatal regions, where they regulate dopamine release and nigrostriatal activity. It is well established that n...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: van Hout M,Klein J,Ahring PK,Brown DT,Thaneshwaran S,Dos Santos AB,Jensen AA,Kohlmeier KA,Christophersen P,Dyhring T

    更新日期:2020-04-01 00:00:00

  • Celecoxib transiently inhibits cellular protein synthesis.

    abstract::To uncover the full spectrum of its pharmacological activities, the selective COX-2 inhibitor celecoxib is routinely being used at concentrations of up to 100 microM in cell culture. At these elevated concentrations, several COX-2-independent effects were identified, although many details of these events have remained...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Pyrko P,Kardosh A,Schönthal AH

    更新日期:2008-01-15 00:00:00

  • Saturation mutagenesis at dihydrofolate reductase codons 22 and 31. A variety of amino acid substitutions conferring methotrexate resistance.

    abstract::Naturally occurring amino acid substitutions conferring resistance to methotrexate (MTX) have been reported previously at codon positions 22 (leu-->arg, phe) and 31 (phe-->ser, trp) of mammalian dihydrofolate reductases (DHFR). To explore the character of other substitutions, a polymerase chain reaction (PCR)-assisted...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Morris JA,McIvor RS

    更新日期:1994-03-29 00:00:00

  • Niacin induces PPARgamma expression and transcriptional activation in macrophages via HM74 and HM74a-mediated induction of prostaglandin synthesis pathways.

    abstract::HM74 and HM74a have been identified as receptors for niacin. HM74a mediates the pharmacological anti-lipolytic effects of niacin in adipocytes by reducing intracellular cyclic AMP (cAMP) and inhibiting release of free fatty acids into the circulation. In macrophages, niacin induces peroxisome proliferator-activated re...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Knowles HJ,te Poele RH,Workman P,Harris AL

    更新日期:2006-02-28 00:00:00

  • Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy.

    abstract::Interleukin-2 (IL-2) has been shown to decrease cytochrome P450 (CYP) mRNAs and proteins in cultured rat hepatocytes, and IL-2 administration decreases CYPs in rats. Although high doses of IL-2 are administered to cancer patients, the effect on human CYPs has not yet been determined. Patients with hepatic metastases f...

    journal_title:Biochemical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Elkahwaji J,Robin MA,Berson A,Tinel M,Lettéron P,Labbe G,Beaune P,Elias D,Rougier P,Escudier B,Duvillard P,Pessayre D

    更新日期:1999-04-15 00:00:00

  • Effects of benfluron and its two metabolites on respiratory processes in P388 murine leukemia and Ehrlich ascites cells.

    abstract::This paper presents data on the effects of benfluron and its two metabolites DBF and NOBF on both endogenous and exogenous, respiration in the presence of succinate as substrate, of both P388 murine leukemia and Ehrlich ascites carcinoma cells. The most efficient inhibitors of endogenous and exogenous respiration were...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Miko M,Krepelka J,Melka M

    更新日期:1991-12-11 00:00:00

  • Metabolic profiling of praziquantel enantiomers.

    abstract::Praziquantel (PZQ), prescribed as a racemic mixture, is the most readily available drug to treat schistosomiasis. In the present study, ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) based metabolomics was employed to decipher ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wang H,Fang ZZ,Zheng Y,Zhou K,Hu C,Krausz KW,Sun D,Idle JR,Gonzalez FJ

    更新日期:2014-07-15 00:00:00

  • Centrally administered orexin prevents lipopolysaccharide and colchicine induced lethality via the vagal cholinergic pathway in a sepsis model in rats.

    abstract::Orexins are neuropeptides implicated in several physiological functions. Accumulating findings suggest a relationship between orexin and sepsis. A recent study demonstrated that orexin acts centrally to improve conditions in sepsis. The present study aims to clarify the precise mechanisms by which central orexin could...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Igarashi S,Nozu T,Ishioh M,Kumei S,Saito T,Toki Y,Hatayama M,Yamamoto M,Shindo M,Tanabe H,Okumura T

    更新日期:2020-12-01 00:00:00

  • Molecular targets for emerging anti-tumor therapies for neurofibromatosis type 1.

    abstract::Neurofibromatosis type 1 (NF1) is the most common cancer predisposition syndrome. NF1 patients present with a constellation of clinical manifestations and have an increased risk of developing certain benign and malignant tumors. This disease results from mutation within the gene encoding neurofibromin, a GTPase activa...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Dilworth JT,Kraniak JM,Wojtkowiak JW,Gibbs RA,Borch RF,Tainsky MA,Reiners JJ Jr,Mattingly RR

    更新日期:2006-11-30 00:00:00

  • Propranolol inhibition of the neutral phospholipases A of rat heart mitochondria, sarcoplasmic reticulum and cytosol.

    abstract::Membrane damage caused by phospholipase A action is thought to be an important factor in ischemic myocardial injury. Propranolol has been shown previously to have beneficial effects in both animal experiments and clinical trials, and it has membrane-stabilizing properties in vitro. To investigate the possibility that ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Trotz M,Jellison EJ,Hostetler KY

    更新日期:1987-12-15 00:00:00

  • PGE2 receptors in detrusor muscle: Drugging the undruggable for urgency.

    abstract::Overactive bladder (OAB) syndrome is a prevalent condition of the lower urinary tract that causes symptoms, such as urinary frequency, urinary urgency, urge incontinence, and nocturia, and disproportionately affects women and the elderly. Current medications for OAB merely provide symptomatic relief with considerable ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Hou R,Yu Y,Jiang J

    更新日期:2020-12-09 00:00:00

  • Bismuth ions inhibit the biological activity of non-amidated gastrins in vivo.

    abstract::The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated gastrins in vitro and in vivo. Bi3+ ions also bind to glycine-extended gastrin17 (Ggly), but inhibit Ggly-induced cell proliferation and migration in gastrointestinal cell lin...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kovac S,Loh SW,Lachal S,Shulkes A,Baldwin GS

    更新日期:2012-02-15 00:00:00

  • Platelet-mediated vascular contractions. Inhibition by flunarizine, a calcium-entry blocker.

    abstract::Flunarizine, a calcium (Ca2+)-entry blocker, selective for vascular tissues, inhibits in a concn-dependent way the contraction of isolated rat caudal artery preparations induced by mediators derived from thrombin-stimulated rat platelets. This inhibition is slow in onset and is of prolonged duration. Specific measurem...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: De Clerck F,Van Nueten JM

    更新日期:1983-03-01 00:00:00

  • Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations.

    abstract::Neuronal nicotinic acetylcholine receptors (nAChR), recognized targets for drug development in cognitive and neuro-degenerative disorders, are allosteric proteins with dynamic interconversions between multiple functional states. Activation of the nAChR ion channel is primarily controlled by the binding of ligands (ago...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Williams DK,Wang J,Papke RL

    更新日期:2011-10-15 00:00:00

  • Inhibitory effect of conjugated eicosapentaenoic acid on mammalian DNA polymerase and topoisomerase activities and human cancer cell proliferation.

    abstract::Conjugated eicosapentaenoic acid (cEPA) selectively inhibited the activities of mammalian DNA polymerases (pols) and human DNA topoisomerases (topos) [Yonezawa Y, Tsuzuki T, Eitsuka T, Miyazawa T, Hada T, Uryu K, et al. Inhibitory effect of conjugated eicosapentaenoic acid on human DNA topoisomerases I and II. Arch Bi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Yonezawa Y,Hada T,Uryu K,Tsuzuki T,Eitsuka T,Miyazawa T,Murakami-Nakai C,Yoshida H,Mizushina Y

    更新日期:2005-08-01 00:00:00

  • Diurnal variation and melatonin induction of hepatic molybdenum hydroxylase activity in the guinea-pig.

    abstract::The activities of the xenobiotic metabolizing enzymes, aldehyde oxidase and xanthine oxidase, were determined in partially purified fractions of adult guinea-pig liver at given times in the day or night. A marked circadian variation in aldehyde oxidase activity was observed with several substrates (phthalazine, phenan...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Beedham C,Padwick DJ,al-Tayib Y,Smith JA

    更新日期:1989-05-01 00:00:00

  • Depletion of a discrete nuclear glutathione pool by oxidative stress, but not by buthionine sulfoximine. Correlation with enhanced alkylating agent cytotoxicity to human melanoma cells in vitro.

    abstract::The existence of a distinct pool of glutathione in the nucleus of cultured human melanoma cells was demonstrated. Melanoma cell nuclei contained 13-35 pmol of glutathione/10(6) nuclei, or approximately 0.4-1.3% of the total cellular glutathione. This nuclear glutathione pool resisted depletion by buthionine sulfoximin...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Jevtović-Todorović V,Guenthner TM

    更新日期:1992-10-06 00:00:00

  • Effects of anti-free radical interventions on phosphatidylcholine hydroperoxide in plasma after ischemia-reperfusion in the liver of rats.

    abstract::The present study set out to investigate whether plasma phosphatidylcholine hydroperoxide (PCOOH) levels could accurately reflect lipid peroxidation linking to liver damage due to ischemia--reperfusion. PCOOH is a primary peroxidative product of phosphatidylcholine (PC), which is the most important functional lipid in...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Takayama F,Egashira T,Kudo Y,Yamanaka Y

    更新日期:1993-11-17 00:00:00

  • Suppressive effects of tranilast on the expression of inducible cyclooxygenase (COX2) in interleukin-1beta-stimulated fibroblasts.

    abstract::We investigated the effects of tranilast on inducible cyclooxygenase (COX2)-mediated prostaglandin E2 (PGE2) production and enzyme induction in interleukin-lbeta (IL-1beta)-stimulated cultured dermal fibroblasts. IL-1beta enhanced PGE2 production in cultured fibroblasts. Tranilast did not affect constitutive cyclooxyg...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Inoue H,Ohshima H,Kono H,Yamanaka M,Kubota T,Aihara M,Hiroi T,Yago N,Ishida H

    更新日期:1997-06-15 00:00:00

  • Hydroxypropyl-beta-cyclodextrin as delivery system for thyroid hormones, regulating glutathione S-transferase expression in rat hepatocyte co-cultures.

    abstract::Thyroid hormones play a role in the regulation of glutathione S-transferase (GST) expression. Here, co-cultures of rat hepatocytes with bile duct epithelial cells have been used to study the direct effects of both triiodothyronine (T3) and thyroxine (T4) on GST activities and proteins. Because T3 and T4 are poorly wat...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Vanhaecke T,Derde MP,Vercruysse A,Rogiers V

    更新日期:2001-05-01 00:00:00

  • Persistent beta-adrenoceptor blockade with alkylating pindolol (BIM) in guinea-pig left atria and trachea.

    abstract::The actions of alkylating pindolol (N8-bromoacetyl-N1-3'-(4-indolyloxy)-2'-hydroxypropyl[z]-1,8- diamino-p-menthane; BIM) have been examined on beta-adrenoceptors in guinea-pig left atria and trachea. In organ bath experiments, addition of BIM (greater than or equal to 0.1 microM), followed by washout, produced concen...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Molenaar P,Russell F,Pitha J,Summers R

    更新日期:1988-10-01 00:00:00

  • The mitochondrial uncoupler dicumarol disrupts the MTT assay.

    abstract::Dicumarol is routinely added to the 3-[4,4-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay to study the role of NAD(P)H:quinone oxido-reductase in drug activation and detoxification. We assessed the direct impact of dicumarol (a mitochondrial uncoupler) on the MTT assay. Mouse mammary tumor (EMT6) an...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Collier AC,Pritsos CA

    更新日期:2003-07-15 00:00:00

  • Deregulated expression of pro-survival and pro-apoptotic p53-dependent genes upon Elongator deficiency in colon cancer cells.

    abstract::Elongator, a multi-subunit complex assembled by the IkappaB kinase-associated protein (IKAP)/hELP1 scaffold protein is involved in transcriptional elongation in the nucleus as well as in tRNA modifications in the cytoplasm. However, the biological processes regulated by Elongator in human cells only start to be elucid...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Cornez I,Creppe C,Gillard M,Hennuy B,Chapelle JP,Dejardin E,Merville MP,Close P,Chariot A

    更新日期:2008-06-01 00:00:00

  • The modulation effect of vitamin E on prostaglandin E2 level and ornithine decarboxylase activity at the promotion phase of lung tumorigenesis in mice.

    abstract::The present study was undertaken to investigate a mechanism of the inhibitory effect of vitamin E in urethane-induced lung tumorigenesis in mice. We assayed ornithine decarboxylase (ODC) activity and the prostaglandin E2 (PGE2) level in lung at 8 weeks after urethane injection (promotion phase). Excessive vitamin E fe...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Yano T,Yano Y,Uchida M,Murakami A,Hagiwara K,Otani S,Ichikawa T

    更新日期:1997-06-01 00:00:00