Publication Abstract from PubMed
The structure of the NAD-dependent oxidoreductase UDP-galactose-4'-epimerase from Trypanosoma brucei in complex with cofactor and the substrate analogue UDP-4-deoxy-4-fluoro-alpha-D-galactose has been determined using diffraction data to 2.7 A resolution. Despite the high level of sequence and structure conservation between the trypanosomatid enzyme and those from humans, yeast and bacteria, the binding of the 4-fluoro-alpha-D-galactose moiety is distinct from previously reported structures. Of particular note is the observation that when bound to the T. brucei enzyme, the galactose moiety of this fluoro-derivative is rotated approximately 180 degrees with respect to the orientation of the hexose component of UDP-glucose when in complex with the human enzyme. The architecture of the catalytic centre is designed to effectively bind different orientations of the hexose, a finding that is consistent with a mechanism that requires the sugar to maintain a degree of flexibility within the active site.
Trypanosoma brucei UDP-galactose-4'-epimerase in ternary complex with NAD+ and the substrate analogue UDP-4-deoxy-4-fluoro-alpha-D-galactose.,Alphey MS, Burton A, Urbaniak MD, Boons GJ, Ferguson MA, Hunter WN Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Sep 1;62(Pt, 9):829-34. Epub 2006 Aug 11. PMID:16946458[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
