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Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase from Leishmania major

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Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase from Leishmania major. / Dickmanns, Achim; Damerow, Sebastian; Neumann, Piotr; Schulz, Eike-Christian; Lamerz, Anne-Christin; Routier, Françoise H; Ficner, Ralf.

In: J MOL BIOL, Vol. 405, No. 2, 14.01.2011, p. 461-78.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Dickmanns, A, Damerow, S, Neumann, P, Schulz, E-C, Lamerz, A-C, Routier, FH & Ficner, R 2011, 'Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase from Leishmania major', J MOL BIOL, vol. 405, no. 2, pp. 461-78. https://doi.org/10.1016/j.jmb.2010.10.057

APA

Dickmanns, A., Damerow, S., Neumann, P., Schulz, E-C., Lamerz, A-C., Routier, F. H., & Ficner, R. (2011). Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase from Leishmania major. J MOL BIOL, 405(2), 461-78. https://doi.org/10.1016/j.jmb.2010.10.057

Vancouver

Dickmanns A, Damerow S, Neumann P, Schulz E-C, Lamerz A-C, Routier FH et al. Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase from Leishmania major. J MOL BIOL. 2011 Jan 14;405(2):461-78. https://doi.org/10.1016/j.jmb.2010.10.057

Bibtex

@article{4b294a6b4e82468688ff21383c9075be,
title = "Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase from Leishmania major",
abstract = "Nucleotide sugars and the enzymes that are responsible for their synthesis are indispensable for the production of complex carbohydrates and, thus, for elaboration of a protective cellular coat for many organisms such as the protozoan parasite Leishmania. These activated sugars are synthesized de novo or derived from salvaged monosaccharides. In addition to UDP-glucose (UDP-Glc) pyrophosphorylase, which catalyzes the formation of UDP-Glc from substrates UTP and glucose-1-phosphate, Leishmania major and plants express a UDP-sugar pyrophosphorylase (USP) that exhibits broad substrate specificity in vitro. The enzyme, likely involved in monosaccharide salvage, preferentially generates UDP-Glc and UDP-galactose, but it may also activate other hexose- or pentose-1-phosphates such as galacturonic acid-1-phosphate or arabinose-1-phosphate. In order to gain insight into structural features governing the differences in substrate specificity, we determined the crystal structure of the L. major USP in the APO-, UTP-, and UDP-sugar-bound conformations. The overall tripartite structure of USP exhibits a significant structural homology to other nucleotidyldiphosphate-glucose pyrophosphorylases. The obtained USP structures reveal the structural rearrangements occurring during the stepwise binding process of the substrates. Moreover, the different product complexes explain the broad substrate specificity of USP, which is enabled by structural changes in the sugar binding region of the active site.",
keywords = "Amino Acid Sequence, Catalysis, Crystallography, X-Ray, Glucosephosphates/metabolism, Leishmania major/enzymology, Models, Molecular, Molecular Sequence Data, Protein Conformation, Sequence Homology, Amino Acid, Substrate Specificity, Sugar Phosphates/metabolism, UTP-Glucose-1-Phosphate Uridylyltransferase/chemistry, Uridine Diphosphate Sugars/metabolism",
author = "Achim Dickmanns and Sebastian Damerow and Piotr Neumann and Eike-Christian Schulz and Anne-Christin Lamerz and Routier, {Fran{\c c}oise H} and Ralf Ficner",
note = "Copyright {\^A}{\textcopyright} 2010 Elsevier Ltd. All rights reserved.",
year = "2011",
month = jan,
day = "14",
doi = "10.1016/j.jmb.2010.10.057",
language = "English",
volume = "405",
pages = "461--78",
journal = "J MOL BIOL",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - Structural basis for the broad substrate range of the UDP-sugar pyrophosphorylase from Leishmania major

AU - Dickmanns, Achim

AU - Damerow, Sebastian

AU - Neumann, Piotr

AU - Schulz, Eike-Christian

AU - Lamerz, Anne-Christin

AU - Routier, Françoise H

AU - Ficner, Ralf

N1 - Copyright © 2010 Elsevier Ltd. All rights reserved.

PY - 2011/1/14

Y1 - 2011/1/14

N2 - Nucleotide sugars and the enzymes that are responsible for their synthesis are indispensable for the production of complex carbohydrates and, thus, for elaboration of a protective cellular coat for many organisms such as the protozoan parasite Leishmania. These activated sugars are synthesized de novo or derived from salvaged monosaccharides. In addition to UDP-glucose (UDP-Glc) pyrophosphorylase, which catalyzes the formation of UDP-Glc from substrates UTP and glucose-1-phosphate, Leishmania major and plants express a UDP-sugar pyrophosphorylase (USP) that exhibits broad substrate specificity in vitro. The enzyme, likely involved in monosaccharide salvage, preferentially generates UDP-Glc and UDP-galactose, but it may also activate other hexose- or pentose-1-phosphates such as galacturonic acid-1-phosphate or arabinose-1-phosphate. In order to gain insight into structural features governing the differences in substrate specificity, we determined the crystal structure of the L. major USP in the APO-, UTP-, and UDP-sugar-bound conformations. The overall tripartite structure of USP exhibits a significant structural homology to other nucleotidyldiphosphate-glucose pyrophosphorylases. The obtained USP structures reveal the structural rearrangements occurring during the stepwise binding process of the substrates. Moreover, the different product complexes explain the broad substrate specificity of USP, which is enabled by structural changes in the sugar binding region of the active site.

AB - Nucleotide sugars and the enzymes that are responsible for their synthesis are indispensable for the production of complex carbohydrates and, thus, for elaboration of a protective cellular coat for many organisms such as the protozoan parasite Leishmania. These activated sugars are synthesized de novo or derived from salvaged monosaccharides. In addition to UDP-glucose (UDP-Glc) pyrophosphorylase, which catalyzes the formation of UDP-Glc from substrates UTP and glucose-1-phosphate, Leishmania major and plants express a UDP-sugar pyrophosphorylase (USP) that exhibits broad substrate specificity in vitro. The enzyme, likely involved in monosaccharide salvage, preferentially generates UDP-Glc and UDP-galactose, but it may also activate other hexose- or pentose-1-phosphates such as galacturonic acid-1-phosphate or arabinose-1-phosphate. In order to gain insight into structural features governing the differences in substrate specificity, we determined the crystal structure of the L. major USP in the APO-, UTP-, and UDP-sugar-bound conformations. The overall tripartite structure of USP exhibits a significant structural homology to other nucleotidyldiphosphate-glucose pyrophosphorylases. The obtained USP structures reveal the structural rearrangements occurring during the stepwise binding process of the substrates. Moreover, the different product complexes explain the broad substrate specificity of USP, which is enabled by structural changes in the sugar binding region of the active site.

KW - Amino Acid Sequence

KW - Catalysis

KW - Crystallography, X-Ray

KW - Glucosephosphates/metabolism

KW - Leishmania major/enzymology

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Protein Conformation

KW - Sequence Homology, Amino Acid

KW - Substrate Specificity

KW - Sugar Phosphates/metabolism

KW - UTP-Glucose-1-Phosphate Uridylyltransferase/chemistry

KW - Uridine Diphosphate Sugars/metabolism

U2 - 10.1016/j.jmb.2010.10.057

DO - 10.1016/j.jmb.2010.10.057

M3 - SCORING: Journal article

C2 - 21073876

VL - 405

SP - 461

EP - 478

JO - J MOL BIOL

JF - J MOL BIOL

SN - 0022-2836

IS - 2

ER -