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.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Urbaniak MD,Yashunsky DV,Crossman A,Nikolaev AV,Ferguson MAdoi
10.1021/cb800143wsubject
Has Abstractpub_date
2008-10-17 00:00:00pages
625-34issue
10eissn
1554-8929issn
1554-8937journal_volume
3pub_type
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