Probing enzymes late in the trypanosomal glycosylphosphatidylinositol biosynthetic pathway with synthetic glycosylphosphatidylinositol analogues

Urbaniak, Michael D. and Yashunsky, Dmitry V. and Crossman, Arthur and Nikolaev, Andrei V. and Ferguson, Michael A. J. (2008) Probing enzymes late in the trypanosomal glycosylphosphatidylinositol biosynthetic pathway with synthetic glycosylphosphatidylinositol analogues. ACS Chemical Biology, 3 (10). pp. 625-634. ISSN 1554-8929

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Abstract

Glycosylphosphatidylinositol (GPI)-anchored proteins are abundant in the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness in humans and the related disease Nagana in cattle, and disruption of GPI biosynthesis is genetically and chemically validated as a drug target. Here, we examine the ability of enzymes of the trypanosomal GPI biosynthetic pathway to recognize and process a series of synthetic dimannosyl-glucosaminylphosphatidylinositol analogues containing systematic modifications on the mannose residues. The data reveal which portions of the natural substrate are important for recognition, explain why mannosylation occurs prior to inositol acylation in the trypanosomal pathway, and identify the first inhibitor of the third alpha-mannosyltransferase of the GPI biosynthetic pathway.

Item Type:
Journal Article
Journal or Publication Title:
ACS Chemical Biology
Additional Information:
ACS Author Choice CC-BY
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1313
Subjects:
ID Code:
66392
Deposited By:
Deposited On:
17 Sep 2013 08:08
Refereed?:
Yes
Published?:
Published
Last Modified:
11 Jul 2020 04:34