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1-46 of 46
Keywords: inhibitor
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Articles
Journal:
Biochemical Journal
Biochem J (2023) 480 (16): 1317–1330.
Published: 25 August 2023
... for OTUD1 lacking the unstructured N-terminal region (OTUD1 OTU + UIM ) in an attempt to identify inhibitors bridging the catalytic domain and the UIM containing region. Two UbVs were identified (UbV OD.1 and UbV OD.2 ) with high affinity and specificity for OTUD1. Of the UbVs identified, UbV OD.1 inhibited...
Includes: Supplementary data
Articles
Ankita Dutta, Ditsa Sarkar, Pooja Murarka, Tasneem Kausar, Satya Narayan, Mohit Mazumder, Sri Rama Koti Ainavarapu, Samudrala Gourinath, Apurba Kumar Sau
Journal:
Biochemical Journal
Biochem J (2021) 478 (4): 871–894.
Published: 24 February 2021
... of inhibitors with greater efficacy. Circular dichroism (CD) spectra of the apo- and Co 2+ -reconstituted wild type and mutant proteins in the far-UV range were recorded on a spectropolarimeter (Chirascan, Applied PhotoPhysics, Leatherhead, U.K.) using a cuvette of 1 mm path length in 20 mM Tris–HCl, pH...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2021) 478 (4): 735–748.
Published: 18 February 2021
... are the two current ‘gold standards’ for enzymatic carbohydrate sulfation analysis. Our study clearly demonstrates the advantages of mobility shift assays for the quantification of near real-time carbohydrate desulfation by purified sulfatases, and will support the search for small molecule inhibitors...
Articles
Daniel M. Foulkes, Keri McLean, Yalin Zheng, Joscelyn Sarsby, Atikah S. Haneef, David G. Fernig, Craig Winstanley, Neil Berry, Stephen B. Kaye
Journal:
Biochemical Journal
Biochem J (2021) 478 (3): 647–668.
Published: 12 February 2021
... therapies. In severe P. aeruginosa infections, the phospholipase activity of the type 3 secretion system toxin, ExoU, induces lysis of target host cells and results in the poorest clinical outcomes. We have developed an integrated pipeline to evaluate small molecule inhibitors of ExoU in vitro...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2021) 478 (2): 389–406.
Published: 27 January 2021
... (PRMT) has been shown to be up-regulated in various cancers. PRMTs have emerged as attractive targets for the development of new cancer therapies. Here, we describe the identification of a natural compound, licochalcone A, as a novel, reversible and selective inhibitor of PRMT6. Since expression...
Includes: Supplementary data
Articles
Pierre Couvineau, Hugo De Almeida, Vincent Leroux, Bernard Roques, Bernard Maigret, Catherine Llorens-Cortes, Xavier Iturrioz
Journal:
Biochemical Journal
Biochem J (2020) 477 (21): 4133–4148.
Published: 05 November 2020
... of blood pressure (BP) in hypertensive animals. The oral administration of RB150 renamed firibastat by WHO, an APA inhibitor prodrug, targeting only the S1 subsite, decreases BP in hypertensive patients from various ethnic origins. To identify new families of potent and selective APA inhibitors, we...
Includes: Supplementary data
Articles
Audrey Colomba, Martina Fitzek, Roger George, Gregory Weitsman, Selene Roberts, Laura Zanetti-Domingues, Michael Hirsch, Daniel J. Rolfe, Shahid Mehmood, Andrew Madin, Jeroen Claus, Svend Kjaer, Ambrosius P. Snijders, Tony Ng, Marisa Martin-Fernandez, David M. Smith, Peter J. Parker
Journal:
Biochemical Journal
Biochem J (2020) 477 (17): 3329–3347.
Published: 10 September 2020
.... As a well-known allosteric activator of epidermal growth factor receptor family members, and playing a major part in cancer progression, the pseudokinase HER3 is a relevant context in which to address the potential of pseudokinases as drug targets for the development of allosteric inhibitors. In this proof...
Includes: Multimedia, Supplementary data
Articles
Dominic P. Byrne, Christopher J. Clarke, Philip J. Brownridge, Anton Kalyuzhnyy, Simon Perkins, Amy Campbell, David Mason, Andrew R. Jones, Patrick A. Eyers, Claire E. Eyers
Journal:
Biochemical Journal
Biochem J (2020) 477 (13): 2451–2475.
Published: 02 July 2020
... kinase inhibitors exemplified by centrinone, which rapidly induces inhibitory effects on PLK4 and leads to on-target centrosome depletion. Despite this, relatively few PLK4 substrates have been identified unequivocally in human cells, and PLK4 signalling outside centriolar networks remains poorly...
Includes: Supplementary data
Articles
Dominic P. Byrne, Yong Li, Krithika Ramakrishnan, Igor L. Barsukov, Edwin A. Yates, Claire E. Eyers, Dulcé Papy-Garcia, Sandrine Chantepie, Vijayakanth Pagadala, Jian Liu, Carrow Wells, David H. Drewry, William J. Zuercher, Neil G. Berry, David G. Fernig, Patrick A. Eyers
Journal:
Biochemical Journal
Biochem J (2018) 475 (15): 2417–2433.
Published: 14 August 2018
... that can be used to quantify the levels of carbohydrate sulfation hampers kinetic analysis of this process and the discovery of HS2ST inhibitors. In the present paper, we describe a new procedure for thermal shift analysis of purified HS2ST. Using this approach, we quantify HS2ST-catalysed oligosaccharide...
Includes: Supplementary data
Articles
Dominic P. Byrne, Matthias Vonderach, Samantha Ferries, Philip J. Brownridge, Claire E. Eyers, Patrick A. Eyers
Journal:
Biochemical Journal
Biochem J (2016) 473 (19): 3159–3175.
Published: 27 September 2016
... populations of the PKA catalytic subunit with distinct structural stability and susceptibility to the physiological protein inhibitor PKI. Native MS of reconstituted PKA R 2 C 2 holoenzymes reveals variable subunit stoichiometry and holoenzyme ablation by PKI binding. Finally, we find that although a ‘kinase...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2016) 473 (18): 2757–2762.
Published: 12 September 2016
... kinase, leucine-rich repeat kinase 2 (LRRK2), which is mutated (and probably hyperactive) in a small, but significant, subset of patients. An exciting new approach for personalised therapy is the development of central nervous system (CNS)-active small-molecule kinase inhibitors, which could be employed...
Articles
Emilie Leroy, Alexandra Dusa, Didier Colau, Amir Motamedi, Xavier Cahu, Céline Mouton, Lily J. Huang, Andrew K. Shiau, Stefan N. Constantinescu
Journal:
Biochemical Journal
Biochem J (2016) 473 (11): 1579–1591.
Published: 27 May 2016
... (NP40) lysis buffer supplemented with orthovanadate, PMSF and protease inhibitor cocktail (ThermoFischer Scientific). Lysate samples were analysed by SDS/PAGE using a 4–12% gradient NuPage® NOVEX BisTris Gel (Invitrogen) and transferred to a nitrocellulose membrane. Total JAK2 was detected using Jak2...
Includes: Supplementary data
Articles
Wei Zhang, Ling Zhai, Yimin Wang, Rebecca J. Boohaker, Wenyan Lu, Vandana V. Gupta, Indira Padmalayam, Robert J. Bostwick, E. Lucile White, Larry J. Ross, Joseph Maddry, Subramaniam Ananthan, Corinne E. Augelli-Szafran, Mark J. Suto, Bo Xu, Rongbao Li, Yonghe Li
Journal:
Biochemical Journal
Biochem J (2016) 473 (8): 1027–1035.
Published: 08 April 2016
... clustering in cancer cells, but is not essential for normal cells. Therefore, targeting KIFC1 may provide novel insight into selective killing of cancer cells. In the present study, we identified a small-molecule KIFC1 inhibitor, SR31527, which inhibited microtubule (MT)-stimulated KIFC1 ATPase activity...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2016) 473 (5): 537.
Published: 24 February 2016
...) isoforms to antagonize TGF-β signalling and TGF-β-induced responses. These findings suggest that sCD109 may play an important role in regulating TGF-β action. binding CD109 glycoprotein inhibitor TGF-β isoforms trap Transforming growth factor-β (TGF-β) is a multifunctional growth factor...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2014) 462 (3): 425–432.
Published: 22 August 2014
... for drug discovery, and inhibitors that target this activity may increase the efficacy of nucleoside/nucleotide analogues, and may help to delay the onset of drug resistance. In the present study, we have developed a FRET (Förster resonance energy transfer)-based high-throughput screening assay for the AZT...
Articles
Hillary F. Allen, Kevin D. Daze, Takashi Shimbo, Anne Lai, Catherine A. Musselman, Jennifer K. Sims, Paul A. Wade, Fraser Hof, Tatiana G. Kutateladze
Journal:
Biochemical Journal
Biochem J (2014) 459 (3): 505–512.
Published: 11 April 2014
... in characterizing functions of methyllysine-recognizing epigenetic readers. Calixarenes disrupt the association of the PHD finger of CHD4 with a trimethylated, but not an unmodified, histone tail. calixarene chromodomain helicase DNA-binding protein 4 (CHD4) histone inhibitor methylation plant...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2013) 456 (1): 1–12.
Published: 24 October 2013
... of these enzymes have resulted in the development of potent and selective inhibitors. The present review gives an overview of these inhibitors and how they have been used on cell lines, primary cells and animals to modulate O -GlcNAc levels and study the effects on signal transduction. 1 To whom...
Articles
Florian Nachon, Eugénie Carletti, Cyril Ronco, Marie Trovaslet, Yvain Nicolet, Ludovic Jean, Pierre-Yves Renard
Journal:
Biochemical Journal
Biochem J (2013) 453 (3): 393–399.
Published: 12 July 2013
... and amyloid aggregation. Such MTDLs are usually on the basis of cholinesterase inhibitors (e.g. tacrine or huprine) coupled with another active molecule aimed at a different target. To aid in the design of these MTDLs, we report the crystal structures of hAChE (human acetylcholinesterase) in complex with FAS...
Articles
Yinghong Gao, Stephen P. Davies, Martin Augustin, Anna Woodward, Umesh A. Patel, Robert Kovelman, Kevin J. Harvey
Journal:
Biochemical Journal
Biochem J (2013) 451 (2): 313–328.
Published: 28 March 2013
...Yinghong Gao; Stephen P. Davies; Martin Augustin; Anna Woodward; Umesh A. Patel; Robert Kovelman; Kevin J. Harvey Despite the development of a number of efficacious kinase inhibitors, the strategies for rational design of these compounds have been limited by target promiscuity. In an effort...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2013) 450 (2): 375–386.
Published: 15 February 2013
... in each well with 100 μl lysis buffer containing protease inhibitors. Protein concentrations were measured using a Bio-Rad Laboratories protein assay kit. Lysates containing 30–80 μg protein were subjected to SDS/PAGE (10 or 12% gels). The separated proteins were transferred on to a nitrocellulose...
Includes: Supplementary data
Articles
Tzu-Yue Shiu, Tien-Yu Huang, Shih-Ming Huang, Yu-Lueng Shih, Heng-Cheng Chu, Wei-Kuo Chang, Tsai-Yuan Hsieh
Journal:
Biochemical Journal
Biochem J (2013) 449 (3): 761–770.
Published: 09 January 2013
...-PCR using a transcription factor activation inhibitor. LPS down-regulated the UGT1A1 mRNA expression in human hepatoma cell lines. A newly identified NF-κB (nuclear factor κB)-binding site was located on the upstream promoter region (−725/−716) of the human UGT1A1 gene. LPS-induced NF-κB activation...
Articles
Journal:
Biochemical Journal
Biochem J (2012) 448 (3): 417–423.
Published: 21 November 2012
...Jin H. Park; Yingting Liu; Mark A. Lemmon; Ravi Radhakrishnan Erlotinib and gefitinib, tyrosine kinase inhibitors used to block EGFR (epidermal growth factor receptor) signalling in cancer, are thought to bind only the active conformation of the EGFR-TKD (tyrosine kinase domain). Through parallel...
Includes: Supplementary data
Articles
Nicholas A. Larsen, Tory J. Nash, Marshall Morningstar, Adam B. Shapiro, Camil Joubran, Carolyn J. Blackett, Arthur D. Patten, P. Ann Boriack-Sjodin, Peter Doig
Journal:
Biochemical Journal
Biochem J (2012) 446 (3): 405–413.
Published: 28 August 2012
... and biophysical characterization showed competition with UTP binding. We determined the crystal structure of a representative aminoquinazoline bound to the Haemophilus influenzae isoenzyme at a resolution of 2.0 Å. The inhibitor occupies part of the UTP site, skirts the outer perimeter of the GlcNAc1-P ( N...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2011) 438 (3): 467–474.
Published: 26 August 2011
... for the action of insecticides. PUGNAc [ O -(2-acetamido-2-deoxy- D -glucopyransylidene)-amino- N -phenylcarbamate] was initially identified as an inhibitor against GH20 β- N -acetyl- D -hexosaminidases. So far no crystal structure of PUGNAc in complex with any GH20 β- N -acetyl- D -hexosaminidase has been...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2011) 437 (1): 135–140.
Published: 14 June 2011
... of F 1 (γ and ϵ) is transferred to the ring of rotor subunits of F o (c subunit ring). ATP-sensitive regulator ATP sensor inhibitor regulation uncoupling The ϵ subunit, the smallest subunit of F 1 , is a known endogenous inhibitor of the ATPase activity of bacterial and chloroplast F...
Articles
Journal:
Biochemical Journal
Biochem J (2010) 425 (3): 531–539.
Published: 15 January 2010
....it ). 24 7 2009 22 10 2009 3 11 2009 3 11 2009 © The Authors Journal compilation © 2010 Biochemical Society 2010 erybraedin C (ERYC) human topoisomerase I inhibition mechanism inhibitor molecular docking pterocarpan EKY3 cells were transformed with YCpGAL1-e...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2006) 399 (1): 47–57.
Published: 13 September 2006
... drug targets. To facilitate a rational drug discovery programme, in the current study we analysed the synthetic substrate and model inhibitor profiles of FP-2 and FP-3 as well as BP-2 (berghepain-2), an orthologue from the rodent parasite Plasmodium berghei . With respect to substrate catalysis, FP-2...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2006) 393 (2): e1.
Published: 23 December 2005
... of basic residues, a specificity that resembles that of the furin-like PCs (proprotein convertases). This led to the demonstration that furin/PC inhibitors containing poly( D -arginine) are also potent inhibitors of NS3, and that anthrax toxin protective antigen and myelin basic protein are potential NS3...
Articles
Journal:
Biochemical Journal
Biochem J (2005) 389 (2): 365–371.
Published: 05 July 2005
... analogue inhibitors. The true transition state, however, has not been structurally characterized. The crystal structure of the C95M/C1095A HIV-1 protease tethered dimer shows a distinctive feature in which the two flaps of the enzyme are in a ‘closed conformation’ even in the unliganded state. This unique...
Articles
Journal:
Biochemical Journal
Biochem J (2005) 387 (3): 585–590.
Published: 26 April 2005
...Alan M. SIMM; E. Joel LOVERIDGE; John CROSBY; Matthew B. AVISON; Timothy R. WALSH; Peter M. BENNETT Bulgecin A, a sulphonated N -acetyl- D -glucosamine unit linked to a 4-hydroxy-5-hydroxymethylproline ring by a β-glycosidic linkage, is a novel type of inhibitor for binuclear metallo-β-lactamases...
Includes: Supplementary data
Articles
Stanley F. BARNETT, Deborah DEFEO-JONES, Sheng FU, Paula J. HANCOCK, Kathleen M. HASKELL, Raymond E. JONES, Jason A. KAHANA, Astrid M. KRAL, Karen LEANDER, Ling L. LEE, John MALINOWSKI, Elizabeth M. McAVOY, Debbie D. NAHAS, Ronald G. ROBINSON, Hans E. HUBER
Journal:
Biochemical Journal
Biochem J (2005) 385 (2): 399–408.
Published: 07 January 2005
... (homogeneous time-resolved fluorescence) assay for Akt kinase activity and screened approx. 270000 compounds for their ability to inhibit the three isoforms of Akt. Two Akt inhibitors were identified that exhibited isoenzyme specificity. The first compound (Akt-I-1) inhibited only Akt1 (IC 50 4.6 μM) while...
Articles
Journal:
Biochemical Journal
Biochem J (2005) 385 (1): 181–187.
Published: 14 December 2004
...Benedykt WLADYKA; Katarzyna PUZIA; Adam DUBIN Staphopain A is a staphylococcal cysteine protease. Genes encoding staphopain A and its specific inhibitor, staphostatin A, are localized in an operon. Staphopain A is an important staphylococcal virulence factor. It is difficult to perform studies...
Articles
Journal:
Biochemical Journal
Biochem J (2004) 384 (2): 201–232.
Published: 23 November 2004
... the fundamental structures of examples from the initiator phase, the pre-mitochondrial regulator phase, the executioner phase, inhibitors and their antagonists, and even the structures of some substrates. The field is as well advanced as the best known of proteolytic pathways, the coagulation cascade...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2004) 381 (3): 735–741.
Published: 27 July 2004
... significant differences in the triclosan-binding region of the P. falciparum enzyme from those of its bacterial counterparts. enoyl-ACP reductase FabI fatty acid biosynthesis (FAS) inhibitor triclosan 1 To whom correspondence should be addressed (e-mail [email protected] ). 26 2...
Includes: Supplementary data
Articles
Journal:
Biochemical Journal
Biochem J (2004) 380 (3): 775–781.
Published: 15 June 2004
... that bind to hK1 with affinity in the nM range and some inhibitors described previously for hK1 were also assayed with mK1 and rK1. 1 To whom correspondence should be addressed (e-mail [email protected] ). 11 7 2003 23 2 2004 25 3 2004 25 3 2004 The Biochemical Society...
Articles
Journal:
Biochemical Journal
Biochem J (2004) 377 (1): 171–181.
Published: 01 January 2004
...Qing-Rong LIU; Ping-Wu ZHANG; Zhicheng LIN; Qi-Fu LI; Amina S. WOODS; Juan TRONCOSO; George R. UHL The activities of PP1 (protein phosphatase 1), a principal cellular phosphatase that reverses serine/threonine protein phosphorylation, can be altered by inhibitors whose activities are themselves...
Articles
Journal:
Biochemical Journal
Biochem J (2003) 373 (2): 523–529.
Published: 15 July 2003
... 2,3,7-trichloro-5-nitroquinoxaline (TNQX) as a potent inhibitor. TNQX showed a potent inhibitory effect, with 50% inhibition at ~1.4 μM, and did not inhibit DNA and RNA polymerases, including retroviral reverse trancriptase. A series of enzyme kinetic experiments suggested that TNQX is a mixed-type non...
Articles
Annemieke J.M. de RUIJTER, Albert H. van GENNIP, Huib N. CARON, Stephan KEMP, André B.P. van KUILENBURG
Journal:
Biochemical Journal
Biochem J (2003) 370 (3): 737–749.
Published: 15 March 2003
... was observed within tissue types. HDAC inhibitors have been shown to induce specific changes in gene expression and to influence a variety of other processes, including growth arrest, differentiation, cytotoxicity and induction of apoptosis. This challenging field has generated many fascinating results which...
Articles
Journal:
Biochemical Journal
Biochem J (2002) 368 (3): 789–797.
Published: 15 December 2002
.... We report the identification of a Drosophila orthologue of nuclear inhibitor of PP1 (NIPP1Dm) through interaction with PP1c in the yeast two-hybrid system. NIPP1Dm shares many properties with mammalian NIPP1 including inhibition of PP1c in vitro , binding to RNA and PP1c, and localization to nuclear...
Includes: Multimedia, Supplementary data
Articles
Arnab Roy CHOWDHURY, Shalini SHARMA, Suparna MANDAL, Anindya GOSWAMI, Sibabrata MUKHOPADHYAY, Hemanta K. MAJUMDER
Journal:
Biochemical Journal
Biochem J (2002) 366 (2): 653–661.
Published: 01 September 2002
... of topoisomerase I by luteolin is due to the stabilization of topoisomerase-I DNA-cleavable complexes. Hence, luteolin is similar to camptothecin, a class I inhibitor, with respect to its ability to form the topoisomerase I-mediated ‘cleavable complex'. But, unlike camptothecin, luteolin interacts with both free...
Articles
Howard R. MELLOR, James NOLAN, Lea PICKERING, Mark R. WORMALD, Frances M. PLATT, Raymond A. DWEK, George W.J. FLEET, Terry D. BUTTERS
Journal:
Biochemical Journal
Biochem J (2002) 366 (1): 225–233.
Published: 15 August 2002
...-mail [email protected] ). 25 3 2002 25 4 2002 1 5 2002 The Biochemical Society, London ©2002 2002 glucosyltransferase hydrophobic imino sugar inhibitor tissue uptake Abbreviations used: DNJ, deoxynojirimycin; MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3...
Articles
Jöelle ROUBY, Martine PUGNIERE, Jean-Claude MANI, Claude GRANIER, Pierrette MONMOUTON, Stephane THEULIER SAINT GERMAIN, Jean-Paul LEONETTI
Journal:
Biochemical Journal
Biochem J (2002) 361 (2): 347–354.
Published: 08 January 2002
... RNA polymerase. One of these mAbs turned out to be the first antibody inhibitor of the binding of NusA and σ70; it did not affect GreB and HepA interactions. Its epitope was located on the β′ subunit at the C-terminus of region G. The properties of this mAb reinforce the idea that the mutually...
Articles
Journal:
Biochemical Journal
Biochem J (2001) 357 (3): 593–615.
Published: 25 July 2001
... in the context of this important part of the enzyme, with its binding sites for iron protoporphyrin IX (haem), biopterin, l -arginine, and the many inhibitors which interact with them. The exact nature of the NOS reaction, its mechanism and its products continue to be sources of controversy. The role...
Articles
Mirjam CZJZEK, Muzaffer CICEK, Véronique ZAMBONI, Wim P. BURMEISTER, David R. BEVAN, Bernard HENRISSAT, Asim ESEN
Journal:
Biochemical Journal
Biochem J (2001) 354 (1): 37–46.
Published: 08 February 2001
... crystallography. In addition, the complex of ZMGlu1 with the non-hydrolysable inhibitor p -nitrophenyl β- d -thioglucoside was crystallized and, based on the partial electron density, a model for the inhibitor molecule within the active site is proposed. The inhibitor is located in a slot-like active site where...
Articles
Journal:
Biochemical Journal
Biochem J (2000) 350 (3): 671–676.
Published: 08 September 2000
... propeptide did not show evidence of forming an active enzyme, of correctly folding in vitro or of inhibiting the active region. folding inhibitor metalloprotease processing pro-enzyme 1 To whom correspondence should be addressed (e-mail [email protected] ). 2 5 2000 28 6...
Articles
Journal:
Biochemical Journal
Biochem J (1999) 343 (1): 29–37.
Published: 24 September 1999
... μ M) and Arg-Ser-Lys-Arg-SC ( K i 11.4 μ M). 1 To whom correspondence should be addressed, at the Ottawa Hospital Medical School (e-mail [email protected] ). 10 5 1999 22 7 1999 The Biochemical Society, London © 1999 1999 inhibitor protease activity protein substrate...