Identification and specificity profiling of protein prenyltransferase inhibitors using new fluorescent phosphoisoprenoids

Journal of the American Chemical Society
Beatrice DursinaKirill Alexandrov

Abstract

Posttranslational modification of proteins with farnesyl and geranylgeranyl isoprenoids is a widespread phenomenon in eukaryotic organisms. Isoprenylation is conferred by three protein prenyltransferases: farnesyl transferase (FTase), geranylgeranyl transferase type-I (GGTase-I), and Rab geranylgeranyltransferase (RabGGTase). Inhibitors of these enzymes have emerged as promising therapeutic compounds for treatment of cancer, viral and parasite originated diseases, as well as osteoporosis. However, no generic nonradioactive protein prenyltransferase assay has been reported to date, complicating identification of enzyme-specific inhibitors. We have addressed this issue by developing two fluorescent analogues of farnesyl and geranylgeranyl pyrophosphates {3,7-dimethyl-8-(7-nitro-benzo[1,2,5]oxadiazol-4-ylamino)-octa-2,6-diene-1}pyrophosphate (NBD-GPP) and {3,7,11-trimethyl-12-(7-nitro-benzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,10-trien-1} pyrophosphate (NBD-FPP), respectively. We demonstrate that these compounds can serve as efficient lipid donors for prenyltransferases. Using these fluorescent lipids, we have developed two simple (SDS-PAGE and bead-based) in vitro prenylation assays applicable to all prenyltransferases. Using the...Continue Reading

References

Apr 21, 1992·Biochemistry·D L PomplianoJ B Gibbs
Jan 1, 1995·Methods in Enzymology·H Mitsuzawa, F Tamanoi
Feb 10, 1995·Analytical Biochemistry·W C PickettS S Kerwar
Jun 16, 1995·The Journal of Biological Chemistry·V K KalmanJ D Robishaw
Mar 8, 1996·The Journal of Biological Chemistry·P J Casey, M C Seabra
Sep 23, 1997·Biochemical and Biophysical Research Communications·G Van DesselA Lagrou
Sep 22, 1999·European Journal of Biochemistry·K AlexandrovR S Goody
Nov 5, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·E K RowinskyD D Von Hoff
Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·L ThaiC J Waechter
Feb 24, 2001·Methods in Enzymology·J H Overmeyer, W A Maltese
May 18, 2001·Biochemical and Biophysical Research Communications·W F MatterC J Vlahos
Aug 18, 2004·The Journal of Experimental Medicine·Gustavo del RealSantos Mañes
Dec 15, 2004·Protein Expression and Purification·Beatrice-Elena DursinaKirill Alexandrov
Dec 17, 2004·Journal of the American Chemical Society·Thomas DurekHerbert Waldmann
Jan 8, 2005·Chembiochem : a European Journal of Chemical Biology·Reinhard ReentsHerbert Waldmann
Feb 15, 1999·Angewandte Chemie·Paul J DysonDavid J Williams

❮ Previous
Next ❯

Citations

Jul 27, 2011·Analytical and Bioanalytical Chemistry·Gudrun Nürenberg, Dietrich A Volmer
Jan 29, 2008·Cancer Metastasis Reviews·Darrell C BessetteCatherine J Pallen
Jul 2, 2009·Journal of Chemical Biology·Edward W Tate
Sep 17, 2011·Chemical Reviews·Howard C Hang, Maurine E Linder
Feb 17, 2009·Nature Chemical Biology·Uyen T T NguyenKirill Alexandrov
Jun 19, 2010·Nature Chemical Biology·Rami N Hannoush, Jinglucy Sun
Jul 12, 2012·Chemical Communications : Chem Comm·Yen-Chih Wang, Mark D Distefano
Mar 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Lena K OesterlinAymelt Itzen
May 20, 2009·The Journal of Biological Chemistry·Robert RucktäschelRalf Erdmann
May 26, 2012·The Journal of Biological Chemistry·Zakir TnimovKirill Alexandrov
Jul 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yao-Wen WuKirill Alexandrov
Oct 31, 2015·International Journal of Molecular Sciences·Jonathan K Dozier, Mark D Distefano
Jul 7, 2015·Plant, Cell & Environment·Christelle DutilleulEric Ducos
Aug 25, 2009·Current Opinion in Chemical Biology·Guillaume CharronHoward C Hang
Oct 7, 2008·Analytical Biochemistry·Jinhwa A ChungT Andrew Taton
Dec 2, 2008·Journal of Cellular and Molecular Medicine·Mihaela PascaruStefan E Szedlacsek
Mar 15, 2012·The FEBS Journal·Pablo RiosMaja Köhn
Sep 4, 2010·Journal of Peptide Science : an Official Publication of the European Peptide Society·Yao-Wen Wu, Roger S Goody
Oct 8, 2014·Biochimica Et Biophysica Acta·Shalise M CouvertierEranthie Weerapana
Sep 17, 2014·Biochemical and Biophysical Research Communications·Zakir TnimovKirill Alexandrov
Aug 11, 2015·Chemical Society Reviews·Ying ZhangHaojie Lu
Mar 25, 2018·Traffic·Guillaume KulakowskiLena K Oesterlin
Nov 26, 2010·Current Protocols in Protein Science·Uyen T T NguyenKirill Alexandrov
Apr 6, 2018·The Journal of Biological Chemistry·Xuefeng ZhangDaniel L Altschuler
Sep 28, 2018·Chemical Society Reviews·Yi ZhangMark D Distefano
May 1, 2010·Chembiochem : a European Journal of Chemical Biology·Uyen T T NguyenKirill Alexandrov
Nov 7, 2006·Chembiochem : a European Journal of Chemical Biology·Yao-Wen WuKirill Alexandrov
Dec 3, 2016·Biochemical Society Transactions·Teresa Rubio, Maja Köhn
Feb 7, 2007·Chembiochem : a European Journal of Chemical Biology·Uyen T T NguyenHerbert Waldmann
Feb 22, 2012·Chembiochem : a European Journal of Chemical Biology·Debapratim DasKirill Alexandrov
Jun 6, 2018·Frontiers in Cellular and Infection Microbiology·Mathilde M CosséAgathe Subtil
Nov 26, 2010·Molecular BioSystems·Guillaume CharronHoward C Hang
Nov 17, 2011·Chembiochem : a European Journal of Chemical Biology·Yao-Wen WuKirill Alexandrov
Jun 24, 2020·ACS Chemical Biology·Sang Hu KimLeah E Cowen
Jan 30, 2008·The Journal of Organic Chemistry·Diwan S RawatRichard A Gibbs
Aug 16, 2008·Journal of the American Chemical Society·Edmund WongSergey N Krylov
Nov 10, 2009·Journal of Medicinal Chemistry·Kui-Thong TanWulf Blankenfeldt

❮ 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.