Leishmania UDP-sugar Pyrophosphorylase. The missing link in galactose salvage?

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Title Leishmania UDP-sugar Pyrophosphorylase. The missing link in galactose salvage?
Author Damerow, Sebastian; Lamerz, Anne-Christin; Haselhorst, Thomas Erwin; Führing, Jana; Zarnovican, Patricia; von Itzstein, Mark; Routier, Françoise H.
Journal Name Journal of Biological Chemistry
Year Published 2010
Place of publication United States
Publisher American Society for Biochemistry and Molecular Biology
Abstract The Leishmania parasite glycocalyx is rich in galactose-containing glycoconjugates that are synthesized by specific glycosyltransferases that use UDP-galactose as a glycosyl donor. UDP-galactose biosynthesis is thought to be predominantly a de novo process involving epimerization of the abundant nucleotide sugar UDP-glucose by the UDP-glucose 4-epimerase, although galactose salvage from the environment has been demonstrated for Leishmania major. Here, we present the characterization of an L. major UDP-sugar pyrophosphorylase able to reversibly activate galactose 1-phosphate into UDP-galactose thus proving the existence of the Isselbacher salvage pathway in this parasite. The ordered bisubstrate mechanism and high affinity of the enzyme for UTP seem to favor the synthesis of nucleotide sugar rather than their pyrophosphorolysis. Although L. major UDP-sugar pyrophosphorylase preferentially activates galactose 1-phosphate and glucose 1-phosphate, the enzyme is able to act on a variety of hexose 1-phosphates as well as pentose 1-phosphates but not hexosamine 1-phosphates and hence presents a broad in vitro specificity. The newly identified enzyme exhibits a low but significant homology with UDP-glucose pyrophosphorylases and conserved in particular is the pyrophosphorylase consensus sequence and residues involved in nucleotide and phosphate binding. Saturation transfer difference NMR spectroscopy experiments confirm the importance of these moieties for substrate binding. The described leishmanial enzyme is closely related to plant UDP-sugar pyrophosphorylases and presents a similar substrate specificity suggesting their common origin.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1074/jbc.M109.067223
Volume 285
Issue Number 2
Page from 878
Page to 887
ISSN 0021-9258
Date Accessioned 2010-11-26
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Medicinal and Biomolecular Chemistry
URI http://hdl.handle.net/10072/36881
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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