Identification, expression and characterisation of a Babesia bovis hexose transporter

Autor: Elvira T. Derbyshire, Charles J. Woodrow, Christophe Morin, Erik de Vries, Sanjeev Krishna, Henry M. Staines, Frits Franssen
Rok vydání: 2008
Předmět:
Oocyte
Erythrocytes
Protozoan Proteins
GLUT1
human facilitative glucose transporter 1
chemistry.chemical_compound
Xenopus laevis
0302 clinical medicine
PCR
polymerase chain reaction
PfHT
Plasmodium falciparum hexose transporter
Cloning
Molecular
PfHT
Cytochalasin B
Peptide sequence
chemistry.chemical_classification
0303 health sciences
biology
3. Good health
Biochemistry
Babesia bovis
Monosaccharide Transport Proteins
030231 tropical medicine
Molecular Sequence Data
PBS
phosphate-buffered saline
Biological Transport
Active
Transport
Article
03 medical and health sciences
Babesiosis
Animals
Humans
Hexose
Molecular Biology
030304 developmental biology
Hexoses
Plasmodium falciparum
Transporter
Sequence Analysis
DNA
biology.organism_classification
Compound 3361
3-O-(undec-10-en)-yl-d-glucose
Molecular biology
Glucose
chemistry
Babesia
biology.protein
GLUT1
Cattle
Parasitology
BboHT1/2
Babesia bovis hexose transporter 1/2
Zdroj: Molecular and Biochemical Parasitology
ISSN: 0166-6851
DOI: 10.1016/j.molbiopara.2008.06.010
Popis: Babesia are tick-transmitted haemoprotozoan parasites that infect cattle, with an estimated 500 million at risk worldwide. Here, two predicted hexose transporters (BboHT1 and 2) have been identified within the Babesia bovis genome. BboHT1, having 40% and 47% amino acid sequence similarity compared with the human (GLUT1) and Plasmodium falciparum (PfHT) hexose transporters, respectively, is the only one that could be characterised functionally after expression in Xenopus laevis oocytes. Radiotracer studies on BboHT1 showed that it is a saturable, Na(+)-independent, stereo-specific hexose transporter, with a K(m) value for glucose of 0.84+/-0.54 mM (mean+/-SEM). Using D-glucose analogues, hydroxyl positions at O-4 and O-6 have been identified as important for ligand binding to BboHT1. D-glucose transport was inhibited maximally by cytochalasin B (50 microM). A long-chain O-3 hexose derivative (compound 3361) that selectively inhibits PfHT also inhibited relatively potently BboHT1, with an apparent K(i) value of 4.1+/-0.9 microM (mean+/-SEM). Compound 3361 did not inhibit B. bovis proliferation in in vitro growth assays but inhibited invasion of glucose-depleted bovine erythrocytes. Taken together with results of inhibition studies with cytochalasin B and beta-glucogallin, these data provide new insights into glucose metabolism of erythrocytic-stage Babesia infections.
Databáze: OpenAIRE
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