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Trypanosoma brucei UDP-galactose-4'-epimerase in ternary complex with NAD+ and the substrate analogue UDP-4-deoxy-4-fluoro-alpha-D-galactose

Research output: Contribution to journalJournal article

Published
  • Magnus S. Alphey
  • Andrew Burton
  • Michael D. Urbaniak
  • Geert-Jan Boons
  • Michael A. J. Ferguson
  • William N. Hunter
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<mark>Journal publication date</mark>1/09/2006
<mark>Journal</mark>Acta Crystallographica Section F: Structural Biology and Crystallization Communications
Issue number9
Volume62
Number of pages6
Pages (from-to)829-834
<mark>State</mark>Published
<mark>Original language</mark>English

Abstract

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.