Abstract
Galactofuranosyltransferases are poorly described enzymes despite their crucial role in the virulence and the pathogenicity of numerous microorganisms. These enzymes are considered as potential targets for therapeutic action. In addition to the only well-characterised prokaryotic GlfT2 from Mycobacterium tuberculosis, four putative genes in Leishmania major were previously described as potential galactofuranosyltransferases. In this study, we have cloned, over-expressed, purified and fully determined the kinetic parameters of these four eukaryotic enzymes, thus demonstrating their unique potency in catalysing the transfer of the galactofuranosyl moiety into acceptors. Their individual promiscuity revealed to be different, as some of them could efficiently use NDP-pyranoses as donor substrates in addition to the natural UDP-galactofuranose. Such results pave the way for the development of chemoenzymatic synthesis of furanosyl-containing glycoconjugates as well as the design of improved drugs against leishmaniasis.
Highlights
Glycosyltransferases (GTs) (E.C. 2.4.x.x) constitute a large class of enzymes involved in the synthesis of abundant complex glycosidic structures expressed in cells[1]
Leishmaniasis belongs to the group of Neglected Tropical Diseases, as defined by World Health Organization (WHO), which includes diseases that are endemic to Third World countries
The genome of Leishmania major was previously screened by Zhang and co-workers, and an analysis led to the identification of four putative genes that could encode for GalfTs, but that share less than 20% similarity of sequence with known GalfTs from other species[30,38]
Summary
Glycosyltransferases (GTs) (E.C. 2.4.x.x) constitute a large class of enzymes involved in the synthesis of abundant complex glycosidic structures expressed in cells[1] These glycoconjugates are of upmost importance for the interaction between cells and for infection by pathogenic species[2]. In Leishmania, galactofuranose-containing glycoconjugates such as lipophosphoglycans (LPGs), glycosylinositolphospholipids (GIPLs) and glycoproteins were reported as playing important role in parasite infection process (Fig. 2)[27,28,29,30]. All these structures have important functions in the parasite lifecycle[31]. We report the first cloning, overexpression, purification and biochemical characterization of these four proteins from L. major as well as the identification of their enzymatic function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
