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Articles

Therapeutic potential of metal ions for COVID-19: insights from the papain-like protease of SARS-CoV-2

In Collection
Coronavirus
Cameron Lee Shetler, Juliana C. Ferreira, Thyago H. S. Cardoso, Edson M.A. Silva, Nitin K. Saksena, Wael M. Rabeh
Journal: Biochemical Journal
Biochem J (2022) 479 (20): 2175–2193.
https://doi.org/10.1042/BCJ20220380
Published: 21 October 2022
... coronavirus 2 (SARS-CoV-2). Papain-like protease (PLpro), one of two cysteine proteases responsible for the maturation and infectivity of SARS-CoV-2, processes and liberates functional proteins from the viral polyproteins and cleaves ubiquitin and ISG15 modifications to inhibit innate immune sensing...
View articletitled, Therapeutic potential of metal ions for COVID-19: insights from the papain-like protease of SARS-CoV-2
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Articles

Diversified amino acid-mediated allosteric regulation of phosphoglycerate dehydrogenase for serine biosynthesis in land plants

Eiji Okamura, Kinuka Ohtaka, Ryuichi Nishihama, Kai Uchida, Ayuko Kuwahara, Keiichi Mochida, Masami Yokota Hirai
Journal: Biochemical Journal
Biochem J (2021) 478 (12): 2217–2232.
https://doi.org/10.1042/BCJ20210191
Published: 18 June 2021
... which is inhibited by l -serine and activated by five proteinogenic amino acids, while the eudicot Arabidopsis thaliana has amino acid-sensitive AtPGDH1 and AtPGDH3 as well as amino acid-insensitive AtPGDH2. In this study, we analyzed PGDH isozymes of the representative land plants: the monocot Oryza...
View articletitled, Diversified amino acid-mediated allosteric regulation of phosphoglycerate dehydrogenase for serine biosynthesis in land plants
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Includes: Supplementary data
Articles

Dissecting capture and twisting of aureolysin and pseudolysin: functional amino acids of the Dispase autolysis-inducing protein

David Fiebig, Anita Anderl, Sahra Al Djaizani, Harald Kolmar, Hans-Lothar Fuchsbauer
Journal: Biochemical Journal
Biochem J (2020) 477 (13): 2595–2606.
https://doi.org/10.1042/BCJ20200407
Published: 17 July 2020
...David Fiebig; Anita Anderl; Sahra Al Djaizani; Harald Kolmar; Hans-Lothar Fuchsbauer The Dispase autolysis-inducing protein (DAIP) from Streptomyces mobaraensis attracts M4 metalloproteases, which results in inhibition and autolysis of bacillolysin (BL) and thermolysin (TL). The present study shows...
View articletitled, Dissecting capture and twisting of aureolysin and pseudolysin: functional amino acids of the Dispase autolysis-inducing protein
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Includes: Supplementary data
Articles

Structural and biochemical evaluation of bisubstrate inhibitors of protein arginine N-methyltransferases PRMT1 and CARM1 (PRMT4)

Emma A. Gunnell, Alaa Al-Noori, Usama Muhsen, Clare C. Davies, James Dowden, Ingrid Dreveny
Journal: Biochemical Journal
Biochem J (2020) 477 (4): 787–800.
https://doi.org/10.1042/BCJ20190826
Published: 27 February 2020
... the Creative Commons Attribution License 4.0 (CC BY) . active site crystallography inhibition PRMT protein arginine methylation small molecules Protein arginine methyltransferases (PRMTs, E.C. 2.1.1.125) catalyse the transfer of methyl groups from S- adenosylmethionine (SAM...
View articletitled, Structural and biochemical evaluation of bisubstrate inhibitors of protein arginine N-methyltransferases PRMT1 and CARM1 (PRMT4)
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Includes: Supplementary data
Articles

Molecular recognition in the product site of cellobiohydrolase Cel7A regulates processive step length

Johan Pelck Olsen, Jeppe Kari, Michael Skovbo Windahl, Kim Borch, Peter Westh
Journal: Biochemical Journal
Biochem J (2020) 477 (1): 99–110.
https://doi.org/10.1042/BCJ20190770
Published: 08 January 2020
... inhibition of Cel7A, but at the same time altered the enzyme product profile and resulted in ∼50% reduction in both processivity and hydrolytic activity. The position of the two arginine residues closely matches the two-fold screw axis symmetry of the substrate, and this energetically favors the productive...
View articletitled, Molecular recognition in the product site of cellobiohydrolase Cel7A regulates processive step length
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Articles

Chemical synthesis and characterization of a new quinazolinedione competitive antagonist for strigolactone receptors with an unexpected binding mode

Cyril Hamiaux, Lesley Larsen, Hui Wen Lee, Zhiwei Luo, Prachi Sharma, Bill C. Hawkins, Nigel B. Perry, Kimberley C. Snowden
Journal: Biochemical Journal
Biochem J (2019) 476 (12): 1843–1856.
https://doi.org/10.1042/BCJ20190288
Published: 28 June 2019
... in silico , highlighting a novel inhibition mechanism for SL receptors. Despite a ∼10-fold difference in potency in vitro , the QADD and tolfenamic acid had comparable activity in planta , suggesting that the QADD compensates for lower potency with increased bioavailability. Altogether, our results...
View articletitled, Chemical synthesis and characterization of a new quinazolinedione competitive antagonist for strigolactone receptors with an unexpected binding mode
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Articles

Multiphasic effect of vinyl pyrrolidone polymers on amyloidogenesis, from macromolecular crowding to inhibition

Richard Berwick, David J. Vaux, Létitia Jean
Journal: Biochemical Journal
Biochem J (2018) 475 (21): 3417–3436.
https://doi.org/10.1042/BCJ20180715
Published: 09 November 2018
... fraction of macromolecules. The resulting macromolecular crowding energetically affects reactions. Amyloidogenesis can either be promoted by macromolecular crowding through the excluded volume effect or inhibited due to a viscosity increase reducing kinetics. Macromolecular crowding can be mimicked...
View articletitled, Multiphasic effect of vinyl pyrrolidone polymers on amyloidogenesis, from macromolecular crowding to inhibition
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Includes: Supplementary data
Articles

Carbidopa: a selective Ah receptor modulator (SAhRM)

Stephen Safe
Journal: Biochemical Journal
Biochem J (2017) 474 (22): 3763–3765.
https://doi.org/10.1042/BCJ20170728
Published: 06 November 2017
..., and this compound inhibits pancreatic cancer cell and tumor growth. These results are consistent with activities of other AhR-active compounds that inhibit carcinogenesis. Like carbidopa, these chemicals are selective AhR modulators with potential clinical applications that are AhR-dependent. Correspondence...
View articletitled, Carbidopa: a selective Ah receptor modulator (SAhRM)
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Articles

A ligand divided: antagonist, agonist and analog control

Daryl E. Klein
Journal: Biochemical Journal
Biochem J (2017) 474 (18): 3087–3088.
https://doi.org/10.1042/BCJ20170495
Published: 31 August 2017
...Daryl E. Klein Inhibiting receptor tyrosine kinases has been a cornerstone of cancer therapeutics for decades. Treatment strategies largely involve small-molecule kinase inhibitors and monoclonal antibodies. For receptors activated by constitutively dimeric ligands, another potential mechanism...
View articletitled, A ligand divided: antagonist, agonist and analog control
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Articles

Quantification of active mitochondrial permeability transition pores using GNX-4975 inhibitor titrations provides insights into molecular identity

Andrew P. Richardson, Andrew P. Halestrap
Journal: Biochemical Journal
Biochem J (2016) 473 (9): 1129–1140.
https://doi.org/10.1042/BCJ20160070
Published: 26 April 2016
...Andrew P. Richardson; Andrew P. Halestrap Inhibition of the mitochondrial permeability transition pore (MPTP) by the novel inhibitor GNX-4975 was characterized. Titration of MPTP activity in de-energized rat liver mitochondria allowed determination of the number of GNX-4975-binding sites...
View articletitled, Quantification of active mitochondrial permeability transition pores using GNX-4975 inhibitor titrations provides insights into molecular identity
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Includes: Supplementary data
Articles

Structural analysis of the diadenylate cyclase reaction of DNA-integrity scanning protein A (DisA) and its inhibition by 3′-dATP

Martina Müller, Tobias Deimling, Karl-Peter Hopfner, Gregor Witte
Journal: Biochemical Journal
Biochem J (2015) 469 (3): 367–374.
https://doi.org/10.1042/BJ20150373
Published: 23 July 2015
... and homology to annotated DAC domains we propose a common mechanism for c-di-AMP synthesis by DAC domains in c-di-AMP-producing species and a possible approach for its effective inhibition. His-tagged T. maritima DisA was cloned and recombinantly expressed as reported previously [ 1 ]. Primers used...
View articletitled, Structural analysis of the diadenylate cyclase reaction of DNA-integrity scanning protein A (DisA) and its inhibition by 3′-dATP
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Includes: Supplementary data
Articles

Identification and characterization of interactions between abscisic acid and mitochondrial adenine nucleotide translocators

Olesya A. Kharenko, Jason Boyd, Ken M. Nelson, Suzanne R. Abrams, Michele C. Loewen
Journal: Biochemical Journal
Biochem J (2011) 437 (1): 117–123.
https://doi.org/10.1042/BJ20101898
Published: 14 June 2011
... mechanisms of ABA action. In the present paper we describe application of a chemical proteomics approach leading to the identification of mitochondrial ANTs (adenine nucleotide translocators) as ABA-interacting proteins. Initial in vitro studies confirmed inhibition of ANT-dependent ATP translocation by ABA...
View articletitled, Identification and characterization of interactions between abscisic acid and mitochondrial adenine nucleotide translocators
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Includes: Supplementary data
Articles

Comparison of the cellular and biochemical properties of Plasmodium falciparum choline and ethanolamine kinases

Blandine Alberge, Leila Gannoun-Zaki, Céline Bascunana, Christophe Tran van Ba, Henri Vial, Rachel Cerdan
Journal: Biochemical Journal
Biochem J (2010) 425 (1): 149–163.
https://doi.org/10.1042/BJ20091119
Published: 14 December 2009
... with a very low affinity. Pf EK was found to be an ethanolamine-specific kinase ( K m =475.7±80.2 μM for ethanolamine). The quaternary ammonium compound hemicholinium-3 and an ethanolamine analogue, 2-amino-1-butanol, selectively inhibited Pf CK or Pf EK. In contrast, the bis-thiazolium compound T3, which...
View articletitled, Comparison of the cellular and biochemical properties of Plasmodium falciparum choline and ethanolamine kinases
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Includes: Supplementary data
Articles

GlcNAcstatins are nanomolar inhibitors of human O -GlcNAcase inducing cellular hyper- O -GlcNAcylation

Helge C. Dorfmueller, Vladimir S. Borodkin, Marianne Schimpl, Daan M. F. van Aalten
Journal: Biochemical Journal
Biochem J (2009) 420 (2): 221–227.
https://doi.org/10.1042/BJ20090110
Published: 13 May 2009
...Helge C. Dorfmueller; Vladimir S. Borodkin; Marianne Schimpl; Daan M. F. van Aalten O -GlcNAcylation is an essential, dynamic and inducible post-translational glycosylation of cytosolic proteins in metazoa and can show interplay with protein phosphorylation. Inhibition of OGA ( O -GlcNAcase...
View articletitled, GlcNAcstatins are nanomolar inhibitors of human O -GlcNAcase inducing cellular hyper- O -GlcNAcylation
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Articles

Identification of essential amino acid residues in a sterol 8,7-isomerase from Zea mays reveals functional homology and diversity with the isomerases of animal and fungal origin

Alain Rahier, Sylvain Pierre, Geneviève Riveill, Francis Karst
Journal: Biochemical Journal
Biochem J (2008) 414 (2): 247–259.
https://doi.org/10.1042/BJ20080292
Published: 12 August 2008
... in relation to the distinct sterol biosynthetic pathways. In accordance with the proposed catalytic mechanism, a series of lipophilic ammonium-ion-containing derivatives possessing a variety of structures and biological properties, potently inhibited the Zm 8,7SI in vitro . To evaluate the importance...
View articletitled, Identification of essential amino acid residues in a sterol 8,7-isomerase from Zea mays reveals functional homology and diversity with the isomerases of animal and fungal origin
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Includes: Supplementary data
Articles

The isolated N-terminal domains of TIMP-1 and TIMP-3 are insufficient for ADAM10 inhibition

Magdalini Rapti, Susan J. Atkinson, Meng-Huee Lee, Andrew Trim, Marcia Moss, Gillian Murphy
Journal: Biochemical Journal
Biochem J (2008) 411 (2): 433–439.
https://doi.org/10.1042/BJ20071430
Published: 27 March 2008
... of metalloproteinases, TIMPs, have proved useful in the study of ADAM function, since TIMP-1 inhibits ADAM10, but not ADAM17; however, both enzymes are inhibited by TIMP-3. In the present study, we show that, in comparison with ADAM17 and the MMPs (matrix metalloproteinases), the N-terminal domains of TIMPs alone...
View articletitled, The isolated N-terminal domains of TIMP-1 and TIMP-3 are insufficient for ADAM10 inhibition
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Articles

Molecules incorporating a benzothiazole core scaffold inhibit the N-myristoyltransferase of Plasmodium falciparum

Paul W. Bowyer, Ruwani S. Gunaratne, Munira Grainger, Chrislaine Withers-Martinez, Sasala R. Wickramsinghe, Edward W. Tate, Robin J. Leatherbarrow, Katherine A. Brown, Anthony A. Holder, Deborah F. Smith
Journal: Biochemical Journal
Biochem J (2007) 408 (2): 173–180.
https://doi.org/10.1042/BJ20070692
Published: 14 November 2007
... Correspondence can be addressed to either of these authors (email [email protected] or [email protected] ). 24 5 2007 14 8 2007 23 8 2007 23 8 2007 © The Authors Journal compilation © 2007 Biochemical Society 2007 benzothiazole codon optimization inhibition N...
View articletitled, Molecules incorporating a benzothiazole core scaffold inhibit the N-myristoyltransferase of Plasmodium falciparum
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Includes: Supplementary data
Articles

Steady-state kinetics and inhibition of anaerobically purified human homogentisate 1,2-dioxygenase

Edwin J. A. VELDHUIZEN, Frédéric H. VAILLANCOURT, Cheryl J. WHITING, Marvin M.-Y. HSIAO, Geneviève GINGRAS, Yufang XIAO, Robert M. TANGUAY, John BOUKOUVALAS, Lindsay D. ELTIS
Journal: Biochemical Journal
Biochem J (2005) 386 (2): 305–314.
https://doi.org/10.1042/BJ20041370
Published: 22 February 2005
...) as a pale yellow powder [mp 70–72 °C; 1 H NMR (300 MHz, CDCl 3 ) δ 11.50 (s, 1H), 6.88 (d, J =2.9 Hz, 1H), 6.70 (d, J =2.9 Hz, 1H), 3.68 (s, 2H); 13 C NMR (75 MHz, CDCl 3 ) δ 172.9, 151.2, 144.8, 125.6, 121.4, 117.8, 115.3, 36.4]. alkaptonuria dioxygenase enzymology homogentisate inhibition...
View articletitled, Steady-state kinetics and inhibition of anaerobically purified human homogentisate 1,2-dioxygenase
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Articles

Novel prenyl-linked benzophenone substrate analogues of mycobacterial mannosyltransferases

Mark R. GUY, Petr A. ILLARIONOV, Sudagar S. GURCHA, Lynn G. DOVER, Kevin J. C. GIBSON, Paul W. SMITH, David E. MINNIKIN, Gurdyal S. BESRA
Journal: Biochemical Journal
Biochem J (2004) 382 (3): 905–912.
https://doi.org/10.1042/BJ20040911
Published: 07 September 2004
..., several inhibited its activity in vitro . The protection of the PPM synthase activity by a ‘natural’ C 75 polyprenyl acceptor during phototreatment is consistent with probe-mediated photoinhibition occurring via specific covalent modification of the enzyme active site. In addition, the unique mannosylated...
View articletitled, Novel prenyl-linked benzophenone substrate analogues of mycobacterial mannosyltransferases
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Articles

Expression and characterization of cathepsin P

Robert W. MASON, Carolyn A. BERGMAN, Guizhen LU, Jennifer FRENCK HOLBROOK, Katia SOL-CHURCH
Journal: Biochemical Journal
Biochem J (2004) 378 (2): 657–663.
https://doi.org/10.1042/bj20031548
Published: 01 March 2004
...2004 2004 activation cathepsin expression inhibition placenta protease Abbreviations used: Dnp, 2,4-dintrophenyl; Dpa, N -3-(2,4-dinitrophenyl)- l -2,3-diaminopropionyl; DTT, dithiothreitol; E-64, trans -epoxysuccinyl- l -leucylamido-(4-guanidino)butane; LC-LC, 6-hexanamido...
View articletitled, Expression and characterization of cathepsin P
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Articles

Beneficial effect of oleoylated lipids on paraoxonase 1: protection against oxidative inactivation and stabilization

S. Duy NGUYEN, Dai-Eun SOK
Journal: Biochemical Journal
Biochem J (2003) 375 (2): 275–285.
https://doi.org/10.1042/bj20030663
Published: 15 October 2003
...S. Duy NGUYEN; Dai-Eun SOK The effect of lipids on PON1 (paraoxonase 1), one of antioxidant proteins in high-density lipoprotein, was investigated in respect to inhibition, protection against oxidative inactivation, and stabilization. When the effect of lipids on the PON1 activity was examined...
View articletitled, Beneficial effect of oleoylated lipids on paraoxonase 1: protection against oxidative inactivation and stabilization
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Articles

Probing the catalytic mechanism of Escherichia coli amine oxidase using mutational variants and a reversible inhibitor as a substrate analogue

Colin G. SAYSELL, Winston S. TAMBYRAJAH, Jeremy M. MURRAY, Carrie M. WILMOT, Simon E.V. PHILLIPS, Michael J. McPHERSON, Peter F. KNOWLES
Journal: Biochemical Journal
Biochem J (2002) 365 (3): 809–816.
https://doi.org/10.1042/bj20011435
Published: 01 August 2002
..., inhibition, topa-quinone, tranylcypromine. was employed in the structural identification of the TPQ cofactor in bovine serum amine oxidase [7]. Amine oxidases are known to be inhibited irreversibly by a number of such compounds, which include PHZ derivatives [17,18], isoniazid [19] and 2-hydrazino- pyridine...
View articletitled, Probing the catalytic mechanism of Escherichia coli amine oxidase using mutational variants and a reversible inhibitor as a substrate analogue
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Articles

Presteady-state kinetics of Bacillus 1,3–1,4-β-glucanase: binding and hydrolysis of a 4-methylumbelliferyl trisaccharide substrate

Mireia ABEL, Antoni PLANAS, Ulla CHRISTENSEN
Journal: Biochemical Journal
Biochem J (2001) 357 (1): 195–202.
https://doi.org/10.1042/bj3570195
Published: 25 June 2001
... 30 3 2001 26 4 2001 The Biochemical Society, London ©2001 2001 fluorescence induced-fit inhibition mechanism stopped-flow Abbreviations used: G4G3G-MU, 4-methylumbelliferyl 3- O -β-cellobiosyl-β- d -glucoside; MU, 4-methylumbelliferone. Biochem. J. (2001) 357, 195...
View articletitled, Presteady-state kinetics of Bacillus 1,3–1,4-β-glucanase: binding and hydrolysis of a 4-methylumbelliferyl trisaccharide substrate
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Articles

Cloning and rational mutagenesis of kexstatin I, a potent proteinaceous inhibitor of Kex2 proteinase

Kohei ODA, Hiroshi OYAMA, Satoshi ITO, Momoko FUKIHARU, Yu MIYAGAWA, Saori TAKAHASHI, Mika HIROSE, Norihisa KIKUCHI, Toru NAKAYAMA, Yuji SHIBANO
Journal: Biochemical Journal
Biochem J (2001) 355 (2): 339–346.
https://doi.org/10.1042/bj3550339
Published: 06 April 2001
... determination and expression of the gene encoding kexstatin I. We also demonstrate its enhanced activity and specificity for Kex2 proteinase inhibition by rational mutagenesis. The cloned kexstatin I gene encoded a protein of 145 amino acid residues, including the 35-residue signal sequence for secretion...
View articletitled, Cloning and rational mutagenesis of kexstatin I, a potent proteinaceous inhibitor of Kex2 proteinase
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Articles

Negative cross-talk between interleukin-3 and interleukin-11 is mediated by suppressor of cytokine signalling-3 (SOCS-3)

Florence MAGRANGEAS, Olivier BOISTEAU, Sébastien DENIS, Yannick JACQUES, Stéphane MINVIELLE
Journal: Biochemical Journal
Biochem J (2001) 353 (2): 223–230.
https://doi.org/10.1042/bj3530223
Published: 08 January 2001
... of STAT3 (signal transducer and activator of transcription 3). This inhibition occurred within 30min and required the synthesis of a negative regulator. The onset of IL-3-dependent inhibition was correlated temporally with the appearance of SOCS-3 (suppressor of cytokine signalling-3) protein. In addition...
View articletitled, Negative cross-talk between interleukin-3 and interleukin-11 is mediated by suppressor of cytokine signalling-3 (SOCS-3)
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Articles

Contrasting effects of N5-substituted tetrahydrobiopterin derivatives on phenylalanine hydroxylase, dihydropteridine reductase and nitric oxide synthase

Ernst R. WERNER, Hans-Jörg HABISCH, Antonius C. F. GORREN, Kurt SCHMIDT, Laura CANEVARI, Gabriele WERNER-FELMAYER, Bernd MAYER
Journal: Biochemical Journal
Biochem J (2000) 348 (3): 579–583.
https://doi.org/10.1042/bj3480579
Published: 07 June 2000
... hydroxylase: N 5 -methyl- and N 5 -hydroxymethyl H 4 biopterin inhibited phenylalanine hydroxylase, whereas N 5 -formyl- and N 5 -acetyl H 4 biopterin had no effect. Our data demonstrate differences in the mechanism of stimulation of phenylalanine hydroxylase and nitric oxide synthase by H 4 biopterin...
View articletitled, Contrasting effects of N5-substituted tetrahydrobiopterin derivatives on phenylalanine hydroxylase, dihydropteridine reductase and nitric oxide synthase
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Articles

Roles of key active-site residues in flavocytochrome P450 BM3

Michael A. NOBLE, Caroline S. MILES, Stephen K. CHAPMAN, Dominikus A. LYSEK, Angela C. MACKAY, Graeme A. REID, Robert P. HANZLIK, Andrew W. MUNRO
Journal: Biochemical Journal
Biochem J (1999) 339 (2): 371–379.
https://doi.org/10.1042/bj3390371
Published: 08 April 1999
... than wild-type. Key words: inhibition, kinetics, mutagenesis. hydroxylase P450cam (CYP 101) and the Bacillus megaterium fatty acid hydroxylase P450 BM3 (CYP 102A1 the structures of both substrate-bound and -free forms have been solved [11,12]. These structures provide templates for modelling eukaryotic...
View articletitled, Roles of key active-site residues in flavocytochrome P450 BM3
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Articles

Synthesis and kinetic evaluation of 4-deoxymaltopentaose and 4-deoxymaltohexaose as inhibitors of muscle and potato α-glucan phosphorylases

Renee MOSI, Stephen G. WITHERS
Journal: Biochemical Journal
Biochem J (1999) 338 (2): 251–256.
https://doi.org/10.1042/bj3380251
Published: 22 February 1999
...-mail [email protected] ). 26 5 1998 29 10 1998 8 12 1998 The Biochemical Society, London © 1999 1999 glycogen glycosyl transferase inhibition oligosaccharide Biochem. J. (1999) 338, 251 256 (Printed in Great Britain) 251 Synthesis and kinetic evaluation of 4...
View articletitled, Synthesis and kinetic evaluation of 4-deoxymaltopentaose and 4-deoxymaltohexaose as inhibitors of muscle and potato α-glucan phosphorylases
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