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Publication Abstract from PubMed

Biosynthesis of the mycobacterial cell wall relies on the activities of many enzymes, including several glycosyltransferases (GTs). The polymerizing galactofuranosyltransferase GlfT2 (Rv3808c) synthesizes the bulk of the galactan portion of the mycolyl-arabinogalactan complex, which is the largest component of the mycobacterial cell wall. We used x-ray crystallography to determine the 2.45-A resolution crystal structure of GlfT2, revealing an unprecedented multidomain structure in which an N-terminal beta-barrel domain and two primarily alpha-helical C-terminal domains flank a central GT-A domain. The kidney-shaped protomers assemble into a C(4)-symmetric homotetramer with an open central core and a surface containing exposed hydrophobic and positively charged residues likely involved with membrane binding. The structure of a 3.1-A resolution complex of GlfT2 with UDP reveals a distinctive mode of nucleotide recognition. In addition, models for the binding of UDP-galactofuranose and acceptor substrates in combination with site-directed mutagenesis and kinetic studies suggest a mechanism that explains the unique ability of GlfT2 to generate alternating beta-(1-->5) and beta-(1-->6) glycosidic linkages using a single active site. The topology imposed by docking a tetrameric assembly onto a membrane bilayer also provides novel insights into aspects of processivity and chain length regulation in this and possibly other polymerizing GTs.

Tetrameric Structure of the GlfT2 Galactofuranosyltransferase Reveals a Scaffold for the Assembly of Mycobacterial Arabinogalactan.,Wheatley RW, Zheng RB, Richards MR, Lowary TL, Ng KK J Biol Chem. 2012 Aug 10;287(33):28132-43. Epub 2012 Jun 15. PMID:22707726^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.