Thursday, September 1, 2011

What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2011 Sep 01
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 - 3 of 3

1. RNA. 2011 Aug 30. [Epub ahead of print]

The crystal structure of an oligo(U):pre-mRNA duplex from a trypanosome RNA editing substrate.

Mooers BH, Singh A.

Source

Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, BRC 466, Oklahoma City, Oklahoma 73104-5419, USA.

Abstract

Guide RNAs bind antiparallel to their target pre-mRNAs to form editing substrates in reaction cycles that insert or delete uridylates (Us) in most mitochondrial transcripts of trypanosomes. The 5' end of each guide RNA has an anchor sequence that binds to the pre-mRNA by base-pair complementarity. The template sequence in the middle of the guide RNA directs the editing reactions. The 3' ends of most guide RNAs have ∼15 contiguous Us that bind to the purine-rich unedited pre-mRNA upstream of the editing site. The resulting U-helix is rich in G·U wobble base pairs. To gain insights into the structure of the U-helix, we crystallized 8 bp of the U-helix in one editing substrate for the A6 mRNA of Trypanosoma brucei. The fragment provides three samples of the 5'-AGA-3'/5'-UUU-3' base-pair triple. The fusion of two identical U-helices head-to-head promoted crystallization. We obtained X-ray diffraction data with a resolution limit of 1.37 Å. The U-helix had low and high twist angles before and after each G·U wobble base pair; this variation was partly due to shearing of the wobble base pairs as revealed in comparisons with a crystal structure of a 16-nt RNA with all Watson-Crick base pairs. Both crystal structures had wider major grooves at the junction between the poly(U) and polypurine tracts. This junction mimics the junction between the template helix and the U-helix in RNA-editing substrates and may be a site of major groove invasion by RNA editing proteins.

PMID:
21878548
[PubMed - as supplied by publisher]
2. BMC Pharmacol. 2011 Aug 30;11(1):9. [Epub ahead of print]

Towards the Development of Novel Trypanosoma brucei RNA Editing Ligase 1 Inhibitors.

Durrant JD, McCammon JA.

Abstract

ABSTRACT:

BACKGROUND:

Trypanosoma brucei (T. brucei) is an infectious agent for which drug development has been largely neglected. We here use a recently developed computer program called AutoGrow to add interacting molecular fragments to S5, a known inhibitor of the validated T. brucei drug target RNA editing ligase 1, in order to improve its predicted binding affinity.

RESULTS:

The proposed binding modes of the resulting compounds mimic that of ATP, the native substrate, and provide insights into novel protein-ligand interactions that may be exploited in future drug-discovery projects.

CONCLUSIONS:

We are hopeful that these new predicted inhibitors will aid medicinal chemists in developing novel therapeutics to fight human African trypanosomiasis.

PMID:
21878090
[PubMed - as supplied by publisher]
3. Trop Biomed. 2011 Apr;28(1):68-75.

Haemoprotozoa of cattle in Northern Kerala, India.

Nair AS, Ravindran R, Lakshmanan B, Kumar SS, Tresamol PV, Saseendranath MR, Senthilvel K, Rao JR, Tewari AK, Ghosh S.

Source

Department of Veterinary Epidemiology and Preventive Medicine, College of Veterinary and Animal Sciences, Mannuthy, Thrissur, Kerala.

Abstract

A cross-sectional study was conducted using 150 blood samples collected from apparently normal / healthy crossbred cattle of Northern Kerala, South India, for detection of haemoprotozoan infections using staining techniques (Giemsa and Acridine Orange) and specific PCR. Theileria like piroplasms and Babesia bigemina were the only protozoan organisms detected in blood smears. Polymerase chain reaction using specific primers revealed amplification of products specific for Trypanosoma evansi (34.6%), Theileria sp. other than T. annulata (16%) and B. bigemina (0.6%). The higher prevalence rate of Trypanosoma evansi indicated that the subclinical parasitism can be due to higher prevalence of tabanid flies. The study also revealed the presence of a theilerial piroplasm other than T. annulata in North Kerala, which needs further investigation.

PMID:
21602771
[PubMed - indexed for MEDLINE]
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