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Global Profiling and Inhibition of Protein Lipidation in Vector and Host Stages of the Sleeping Sickness Parasite Trypanosoma brucei

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Global Profiling and Inhibition of Protein Lipidation in Vector and Host Stages of the Sleeping Sickness Parasite Trypanosoma brucei. / Wright, Megan H; Paape, Daniel; Price, Helen P; Smith, Deborah F; Tate, Edward W.

In: BMC Infectious Diseases, Vol. 2, No. 6, 10.06.2016, p. 427-441.

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Harvard

Wright, MH, Paape, D, Price, HP, Smith, DF & Tate, EW 2016, 'Global Profiling and Inhibition of Protein Lipidation in Vector and Host Stages of the Sleeping Sickness Parasite Trypanosoma brucei', BMC Infectious Diseases, vol. 2, no. 6, pp. 427-441. https://doi.org/10.1021/acsinfecdis.6b00034

APA

Wright, M. H., Paape, D., Price, H. P., Smith, D. F., & Tate, E. W. (2016). Global Profiling and Inhibition of Protein Lipidation in Vector and Host Stages of the Sleeping Sickness Parasite Trypanosoma brucei. BMC Infectious Diseases, 2(6), 427-441. https://doi.org/10.1021/acsinfecdis.6b00034

Vancouver

Wright MH, Paape D, Price HP, Smith DF, Tate EW. Global Profiling and Inhibition of Protein Lipidation in Vector and Host Stages of the Sleeping Sickness Parasite Trypanosoma brucei. BMC Infectious Diseases. 2016 Jun 10;2(6):427-441. https://doi.org/10.1021/acsinfecdis.6b00034

Author

Wright, Megan H ; Paape, Daniel ; Price, Helen P ; Smith, Deborah F ; Tate, Edward W. / Global Profiling and Inhibition of Protein Lipidation in Vector and Host Stages of the Sleeping Sickness Parasite Trypanosoma brucei. In: BMC Infectious Diseases. 2016 ; Vol. 2, No. 6. pp. 427-441.

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@article{bcf90c6a574b428a9f21c5769fa071e6,
title = "Global Profiling and Inhibition of Protein Lipidation in Vector and Host Stages of the Sleeping Sickness Parasite Trypanosoma brucei",
abstract = "The enzyme N-myristoyltransferase (NMT) catalyzes the essential fatty acylation of substrate proteins with myristic acid in eukaryotes and is a validated drug target in the parasite Trypanosoma brucei, the causative agent of African trypanosomiasis (sleeping sickness). N-Myristoylation typically mediates membrane localization of proteins and is essential to the function of many. However, only a handful of proteins are experimentally validated as N-myristoylated in T. brucei. Here, we perform metabolic labeling with an alkyne-tagged myristic acid analogue, enabling the capture of lipidated proteins in insect and host life stages of T. brucei. We further compare this with a longer chain palmitate analogue to explore the chain length-specific incorporation of fatty acids into proteins. Finally, we combine the alkynyl-myristate analogue with NMT inhibitors and quantitative chemical proteomics to globally define N-myristoylated proteins in the clinically relevant bloodstream form parasites. This analysis reveals five ARF family small GTPases, calpain-like proteins, phosphatases, and many uncharacterized proteins as substrates of NMT in the parasite, providing a global view of the scope of this important protein modification and further evidence for the crucial and pleiotropic role of NMT in the cell.",
keywords = "Journal Article",
author = "Wright, {Megan H} and Daniel Paape and Price, {Helen P} and Smith, {Deborah F} and Tate, {Edward W}",
note = "{\textcopyright} 2016, American Chemical Society.",
year = "2016",
month = jun,
day = "10",
doi = "10.1021/acsinfecdis.6b00034",
language = "English",
volume = "2",
pages = "427--441",
journal = "BMC Infectious Diseases",
issn = "1471-2334",
publisher = "BioMed Central",
number = "6",

}

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TY - JOUR

T1 - Global Profiling and Inhibition of Protein Lipidation in Vector and Host Stages of the Sleeping Sickness Parasite Trypanosoma brucei

AU - Wright, Megan H

AU - Paape, Daniel

AU - Price, Helen P

AU - Smith, Deborah F

AU - Tate, Edward W

N1 - © 2016, American Chemical Society.

PY - 2016/6/10

Y1 - 2016/6/10

N2 - The enzyme N-myristoyltransferase (NMT) catalyzes the essential fatty acylation of substrate proteins with myristic acid in eukaryotes and is a validated drug target in the parasite Trypanosoma brucei, the causative agent of African trypanosomiasis (sleeping sickness). N-Myristoylation typically mediates membrane localization of proteins and is essential to the function of many. However, only a handful of proteins are experimentally validated as N-myristoylated in T. brucei. Here, we perform metabolic labeling with an alkyne-tagged myristic acid analogue, enabling the capture of lipidated proteins in insect and host life stages of T. brucei. We further compare this with a longer chain palmitate analogue to explore the chain length-specific incorporation of fatty acids into proteins. Finally, we combine the alkynyl-myristate analogue with NMT inhibitors and quantitative chemical proteomics to globally define N-myristoylated proteins in the clinically relevant bloodstream form parasites. This analysis reveals five ARF family small GTPases, calpain-like proteins, phosphatases, and many uncharacterized proteins as substrates of NMT in the parasite, providing a global view of the scope of this important protein modification and further evidence for the crucial and pleiotropic role of NMT in the cell.

AB - The enzyme N-myristoyltransferase (NMT) catalyzes the essential fatty acylation of substrate proteins with myristic acid in eukaryotes and is a validated drug target in the parasite Trypanosoma brucei, the causative agent of African trypanosomiasis (sleeping sickness). N-Myristoylation typically mediates membrane localization of proteins and is essential to the function of many. However, only a handful of proteins are experimentally validated as N-myristoylated in T. brucei. Here, we perform metabolic labeling with an alkyne-tagged myristic acid analogue, enabling the capture of lipidated proteins in insect and host life stages of T. brucei. We further compare this with a longer chain palmitate analogue to explore the chain length-specific incorporation of fatty acids into proteins. Finally, we combine the alkynyl-myristate analogue with NMT inhibitors and quantitative chemical proteomics to globally define N-myristoylated proteins in the clinically relevant bloodstream form parasites. This analysis reveals five ARF family small GTPases, calpain-like proteins, phosphatases, and many uncharacterized proteins as substrates of NMT in the parasite, providing a global view of the scope of this important protein modification and further evidence for the crucial and pleiotropic role of NMT in the cell.

KW - Journal Article

U2 - 10.1021/acsinfecdis.6b00034

DO - 10.1021/acsinfecdis.6b00034

M3 - Article

C2 - 27331140

VL - 2

SP - 427

EP - 441

JO - BMC Infectious Diseases

JF - BMC Infectious Diseases

SN - 1471-2334

IS - 6

ER -