What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2009 Nov 19
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

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1.	Biochem J. 2009 Nov 18. [Epub ahead of print] GDP-Mannose pyrophosphorylase is essential in the bloodstream form of Trypanosoma brucei. Denton H, Fyffe S, Smith TK. A putative guanidine diphosphomannose pyrophophosphorylase (GDP-Man PP) gene from Trypanosoma brucei was identified in the genome and subsequently cloned, sequenced, and recombinantly expressed and shown to be a catalytically active dimer. Kinetic analysis revealed a Vmax of 0.34 mumol / min/ mg and Km's of 67 muM and 12 muM for GTP and mannose-1-phosphate respectively. Further kinetic studies showed GDP-Man was a potent product feedback inhibitor. RNAi of the cytosolic TbGDP-Man PP showed mRNA levels were reduced to ~20% of wild type levels, causing the cells to die after 3-4 days, demonstrating TbGDP-Man PP is essential in the bloodstream form of T.brucei and thus a potential drug target. The RNAi induced parasites have a greatly reduced capability to form GDP-Man, leading ultimately to a reduction in their ability to synthesize their essential glycosylphosphatidylinositol anchors. The RNAi induced parasites also showed aberrant N-glycosylation of their major cell-surface glycoprotein, variant surface glycoprotein, with loss of the high mannose Man9GlcNAc2 N-glycosylation at Asn-428 and formation of complex N-glycans at the Asn-263.
	PMID: 19919534 [PubMed - as supplied by publisher]