Molecular mechanisms underlying he interaction of motuporin and microcystins with type-1 and type-2A protein phosphatases

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
M CraigC E Holmes

Abstract

Heptapeptide microcystin and pentapeptide motuporin (nodularin-V) are equipotent inhibitors of type-1 and type-2A protein phosphatase catalytic subunits (PP-1c and PP-2Ac). Herein we describe elucidation of the molecular mechanisms involved in the interaction of these structurally similar hepatotoxins with PP-1c/PP-2Ac and identification of an important functional difference between their mode of interaction with these enzymes. Microcystin-LR, microcystin-LA, and microcystin-LL were found to interact with PP-2Ac and PP-1c by a two-step mechanism involving rapid binding and inactivation of the protein phosphatase (PPase) catalytic subunit, followed by a slower covalent interaction (within hours). Covalent adducts comprising PPase-toxin complexes were separated from free PPase by C-18 reverse-phase liquid chromatography, thus allowing the time course of covalent adduct formation to be quantitated. In contrast to microcystins, motuporin (nodularin-V) and nodularin-R were unable to form covalent complexes with either PP-1c or PP-2Ac even after 96 h incubation. Specific reduction of microcystin-LA to dihydromicrocystin-LA abolished the ability of the toxin to form a covalent adduct with PP-2Ac. Specific methyl esterification of the ...Continue Reading

References

Jun 1, 1992·The Journal of Applied Bacteriology·W W Carmichael
Sep 1, 1991·Japanese Journal of Cancer Research : Gann·R Nishiwaki-MatsushimaH Fujiki
Jan 1, 1991·Journal of Biochemical Toxicology·N A RobinsonJ G Pace
Jan 1, 1990·Journal of Cancer Research and Clinical Oncology·S YoshizawaH Fujiki
Dec 31, 1990·Biochemical and Biophysical Research Communications·J E ErikssonD Hartshorne
Feb 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·T KrishnamurthyS Missler
Jan 1, 1988·Toxicon : Official Journal of the International Society on Toxinology·W W CarmichaelR E Moore
Nov 2, 1995·Biochemical and Biophysical Research Communications·M RunnegarL Zhang
Feb 1, 1995·Nature Structural Biology·J R BaguC F Holmes
Dec 1, 1993·Toxicon : Official Journal of the International Society on Toxinology·M CraigC F Holmes
Dec 1, 1995·Current Opinion in Structural Biology·D Barford

❮ Previous
Next ❯

Citations

Jun 21, 2001·Environmental Toxicology·J MankiewiczM Zalewski
Mar 23, 2004·Toxicon : Official Journal of the International Society on Toxinology·Christelle MalbrouckPatrick Kestemont
Mar 20, 2013·Toxicon : Official Journal of the International Society on Toxinology·Daniela SedanDarío Andrinolo
Jun 1, 2001·Toxicon : Official Journal of the International Society on Toxinology·J McElhineyC Leifert
Feb 5, 2003·Toxicon : Official Journal of the International Society on Toxinology·Lisa SpoofJussi Meriluoto
Feb 5, 2003·Toxicon : Official Journal of the International Society on Toxinology·Pia S M Vesterkvist, Jussi A O Meriluoto
Jan 15, 1998·Toxicon : Official Journal of the International Society on Toxinology·D E WilliamsC F Holmes
Mar 10, 2000·International Journal of Immunopharmacology·W BaierK Mittenbühler
Apr 22, 1999·General Pharmacology·S HarrisonD Spina
Jun 5, 2003·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Christelle MalbrouckPatrick Kestemont
Apr 30, 2013·Chemical Research in Toxicology·Dariusz DzigaJussi Meriluoto
Jun 5, 2012·The Journal of Biological Chemistry·Cindy Sutherland, Michael P Walsh
Mar 4, 2000·Environmental Health Perspectives·B C HitzfeldD R Dietrich
Feb 18, 2010·International Journal of Molecular Sciences·Alexandre Campos, Vitor Vasconcelos
Jan 25, 2012·International Journal of Molecular Sciences·José Carlos MartinsVitor Vasconcelos
Apr 23, 2010·Marine Drugs·Ioannis SainisEvangelos Briasoulis
Feb 7, 2001·Biochemical and Biophysical Research Communications·J F DawsonC F Holmes
Mar 7, 2014·Toxicon : Official Journal of the International Society on Toxinology·L J MattosR M Soares
Sep 11, 2014·Chemico-biological Interactions·Alexandra H HeussnerDaniel R Dietrich
Nov 26, 2009·Bulletin of Environmental Contamination and Toxicology·Dawen ZhangJun Chen
Dec 30, 2015·Chemical Research in Toxicology·Kyung KooJohn R Porter
May 15, 2012·Toxicology Letters·Yuan ZhouXiaodong Han
Jan 5, 2010·Ecotoxicology and Environmental Safety·Issam El GhazaliVitor Vasconcelos
Jan 15, 2010·Ecotoxicology and Environmental Safety·Juliette L SmithGregory L Boyer
Oct 23, 2015·Environmental Science and Pollution Research International·Xiaochun GuoCheng Zeng
Aug 14, 2013·The FEBS Journal·Mengmeng ZhangYan Zhang
Nov 9, 2004·Toxicon : Official Journal of the International Society on Toxinology·Christelle MalbrouckPatrick Kestemont
Jul 25, 2006·Toxicon : Official Journal of the International Society on Toxinology·R Jayaraj, P V Lakshmana Rao
Nov 2, 2015·Journal of Hazardous Materials·Liang ChenPing Xie
Feb 5, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Marisa FreitasVitor Vasconcelos
Nov 26, 2011·Toxicon : Official Journal of the International Society on Toxinology·S M K NybomJ A O Meriluoto
Mar 16, 2017·The Journal of Organic Chemistry·Ivan ZemskovValentin Wittmann
Jun 28, 2016·Chemistry : a European Journal·Ivan ZemskovValentin Wittmann
Aug 25, 2006·Toxicon : Official Journal of the International Society on Toxinology·Juliette L Smith, James F Haney
Nov 13, 2003·Chembiochem : a European Journal of Chemical Biology·Hao ZhouWilfred A van der Donk

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.