Tuesday, December 29, 2009

What's new for 'Trypanosomatids' in PubMed

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Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results
Items 1 -2 of 2

1. J Mol Biol. 2009 Dec 23. [Epub ahead of print]

N-myristoyltransferase from Leishmania donovani: Structural and Functional Characterisation of a Potential Drug Target for Visceral Leishmaniasis.

Brannigan JA, Smith BA, Yu Z, Brzozowski AM, Hodgkinson MR, Maroof A, Price HP, Meier F, Leatherbarrow RJ, Tate EW, Smith DF, Wilkinson AJ.

York Structural Biology Laboratory, Department of Chemistry, York YO10 5YW, UK.

N-myristoyltransferase (NMT) catalyses the attachment of the 14-carbon saturated fatty acid, myristate, to the amino terminal glycine residue of a subset of eukaryotic proteins that function in multiple cellular processes, including vesicular protein trafficking and signal transduction. In these pathways, N-myristoylation facilitates association of substrate proteins with membranes or the hydrophobic domains of other partner peptides. NMT function is essential for viability in all cell types tested to date, demonstrating that this enzyme has potential as a target for drug development. Here, we provide genetic evidence that NMT is likely to be essential for viability in insect stages of the pathogenic protozoan parasite, Leishmania donovani, causative agent of the tropical infectious disease, visceral leishmaniasis. The open reading frame of L. donovani NMT has been amplified and used to overproduce active recombinant enzyme in E. coli, as demonstrated by gel mobility shift assays of ligand binding and peptide-myristoylation activity in scintillation proximity assays. The purified protein has been crystallized in complex with the non-hydrolysable substrate analogue S-(2-oxo)pentadecyl-CoA, and its structure solved by molecular replacement at 1.4 A resolution. The structure has as its defining feature a 14-stranded twisted beta-sheet on which helices are packed so as to form an extended and curved substrate-binding groove running across two protein lobes. The fatty acyl-CoA is largely buried in the amino terminal lobe, its binding leading to the loosening of a flap, which in unliganded NMT structures, occludes the protein substrate binding site in the carboxyl terminal lobe. These studies validate LdNMT as a potential target for development of new therapeutic agents against visceral leishmaniasis. Copyright © 2009. Published by Elsevier Ltd.

PMID: 20036251 [PubMed - as supplied by publisher]
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2. Wien Klin Wochenschr. 2009 Oct;121 Suppl 3:42-5.

Detection of Babesia canis subspecies and other arthropod-borne diseases in dogs from Tirana, Albania.

Hamel D, Silaghi C, Knaus M, Visser M, Kusi I, Rapti D, Rehbein S, Pfister K.

Chair of Comparative Tropical Medicine and Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Munich, Germany. dietmar.hamel@tropa.vetmed.uni-muenchen.de

Summary. The importance of arthropod-borne diseases increased in the recent past in particular due to frequent travel with dogs in or by importing of dogs from regions with endemic occurrence of these diseases. While the epidemiological situation is well known for the western parts of the Mediterranean, only limited data is available for Eastern Europe and the Balkans. Thirty clinically healthy dogs from suburban areas of Tirana, Albania, were tested for Babesia canis, Hepatozoon spp., Leishmania spp., Dirofilaria spp., Ehrlichia canis, Anaplasma phagocytophilum, Bartonella spp. and Rickettsia spp. using direct and indirect methods. Antibodies against and/or pathogens of arthropod-borne diseases were detected in the blood of 20 (67%) dogs. Nineteen dogs (63%) had antibodies against B. canis, E. canis and/or A. phagocytophilum. Babesia c. canis, Babesia c. vogeli, Hepatozoon spp., D. immitis and/or E. canis were identified by blood smear, PCR or ELISA in 13 (43%) dogs. There was no evidence for Leishmania spp., Bartonella spp. and Rickettsia spp. infections.

PMID: 19915816 [PubMed - in process]
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