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Identification, subcellular localization, biochemical properties, and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase

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Identification, subcellular localization, biochemical properties, and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase. / Marino, Karina; Guther, Maria Lucia Sampaio; Wernimont, Amy K.; Amani, Mernhaz; Hui, Raymond; Ferguson, Michael A. J.

In: Glycobiology, Vol. 20, No. 12, 12.2010, p. 1619-1630.

Research output: Contribution to journalArticle

Harvard

Marino, K, Guther, MLS, Wernimont, AK, Amani, M, Hui, R & Ferguson, MAJ 2010, 'Identification, subcellular localization, biochemical properties, and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase' Glycobiology, vol 20, no. 12, pp. 1619-1630.

APA

Marino, K., Guther, M. L. S., Wernimont, A. K., Amani, M., Hui, R., & Ferguson, M. A. J. (2010). Identification, subcellular localization, biochemical properties, and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase. Glycobiology, 20(12), 1619-1630doi: 10.1093/glycob/cwq115

Vancouver

Marino K, Guther MLS, Wernimont AK, Amani M, Hui R, Ferguson MAJ. Identification, subcellular localization, biochemical properties, and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase. Glycobiology. 2010 Dec;20(12):1619-1630.

Author

Marino, Karina; Guther, Maria Lucia Sampaio; Wernimont, Amy K.; Amani, Mernhaz; Hui, Raymond; Ferguson, Michael A. J. / Identification, subcellular localization, biochemical properties, and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase.

In: Glycobiology, Vol. 20, No. 12, 12.2010, p. 1619-1630.

Research output: Contribution to journalArticle

Bibtex - Download

@article{fc16ec2b716a4abcbfff6beeeebf7cf1,
title = "Identification, subcellular localization, biochemical properties, and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase",
author = "Karina Marino and Guther, {Maria Lucia Sampaio} and Wernimont, {Amy K.} and Mernhaz Amani and Raymond Hui and Ferguson, {Michael A. J.}",
year = "2010",
volume = "20",
number = "12",
pages = "1619--1630",
journal = "Glycobiology",
issn = "0959-6658",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Identification, subcellular localization, biochemical properties, and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase

A1 - Marino,Karina

A1 - Guther,Maria Lucia Sampaio

A1 - Wernimont,Amy K.

A1 - Amani,Mernhaz

A1 - Hui,Raymond

A1 - Ferguson,Michael A. J.

AU - Marino,Karina

AU - Guther,Maria Lucia Sampaio

AU - Wernimont,Amy K.

AU - Amani,Mernhaz

AU - Hui,Raymond

AU - Ferguson,Michael A. J.

PY - 2010/12

Y1 - 2010/12

N2 - <p>The protozoan parasite Trypanosoma brucei is the causative agent of the cattle disease Nagana and human African sleeping sickness. Glycoproteins play key roles in the parasite's survival and infectivity, and the de novo biosyntheses of the sugar nucleotides UDP-galactose (UDP-Gal), UDP-N-acetylglucosamine, and GDP-fucose have been shown to be essential for their growth. The only route to UDP-Gal in T. brucei is through the epimerization of UDP-glucose (UDP-Glc) by UDP-Glc 4'-epimerase. UDP-Glc is also the glucosyl donor for the unfolded glycoprotein glucosyltransferase (UGGT) involved in glycoprotein quality control in the endoplasmic reticulum and is the presumed donor for the synthesis of base J (beta-D-glucosylhydroxymethyluracil), a rare deoxynucleotide found in telomereproximal DNA in the bloodstream form of T. brucei. Considering that UDP-Glc plays such a central role in carbohydrate metabolism, we decided to characterize UDP-Glc biosynthesis in T. brucei. We identified and characterized the parasite UDP-glucose pyrophosphorylase (TbUGP), responsible for the formation of UDP-Glc from glucose-1-phosphate and UTP, and localized the enzyme to the peroxisome-like glycosome organelles of the parasite. Recombinant TbUGP was shown to be enzymatically active and specific for glucose-1-phosphate. The high-resolution crystal structure was also solved, providing a framework for the design of potential inhibitors against the parasite enzyme.</p>

AB - <p>The protozoan parasite Trypanosoma brucei is the causative agent of the cattle disease Nagana and human African sleeping sickness. Glycoproteins play key roles in the parasite's survival and infectivity, and the de novo biosyntheses of the sugar nucleotides UDP-galactose (UDP-Gal), UDP-N-acetylglucosamine, and GDP-fucose have been shown to be essential for their growth. The only route to UDP-Gal in T. brucei is through the epimerization of UDP-glucose (UDP-Glc) by UDP-Glc 4'-epimerase. UDP-Glc is also the glucosyl donor for the unfolded glycoprotein glucosyltransferase (UGGT) involved in glycoprotein quality control in the endoplasmic reticulum and is the presumed donor for the synthesis of base J (beta-D-glucosylhydroxymethyluracil), a rare deoxynucleotide found in telomereproximal DNA in the bloodstream form of T. brucei. Considering that UDP-Glc plays such a central role in carbohydrate metabolism, we decided to characterize UDP-Glc biosynthesis in T. brucei. We identified and characterized the parasite UDP-glucose pyrophosphorylase (TbUGP), responsible for the formation of UDP-Glc from glucose-1-phosphate and UTP, and localized the enzyme to the peroxisome-like glycosome organelles of the parasite. Recombinant TbUGP was shown to be enzymatically active and specific for glucose-1-phosphate. The high-resolution crystal structure was also solved, providing a framework for the design of potential inhibitors against the parasite enzyme.</p>

KW - kinetoplastids

KW - sugar nucleotide metabolism

KW - Trypanosoma brucei

KW - UDP-glucose

KW - UDP-glucose pyrophosphorylase

KW - AFRICAN SLEEPING SICKNESS

KW - LEISHMANIA-MAJOR

KW - UDPGLUCOSE PYROPHOSPHORYLASE

KW - GALACTOSE METABOLISM

KW - N-ACETYLGLUCOSAMINE

KW - MOLECULAR-CLONING

KW - LIGAND-BINDING

KW - CELL-GROWTH

KW - LIVER

KW - GLYCOPROTEIN

U2 - 10.1093/glycob/cwq115

DO - 10.1093/glycob/cwq115

M1 - Article

JO - Glycobiology

JF - Glycobiology

SN - 0959-6658

IS - 12

VL - 20

SP - 1619

EP - 1630

ER -

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