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

Alphey, Magnus S. and Burton, Andrew and Urbaniak, Michael D. and Boons, Geert-Jan and Ferguson, Michael A. J. and Hunter, William N. (2006) Trypanosoma brucei UDP-galactose-4'-epimerase in ternary complex with NAD+ and the substrate analogue UDP-4-deoxy-4-fluoro-alpha-D-galactose. Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 62 (9). pp. 829-834.

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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.

Item Type:
Journal Article
Journal or Publication Title:
Acta Crystallographica Section F: Structural Biology and Crystallization Communications
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1303
Subjects:
?? animalscatalytic domaincrystallography, x-raynadprotein structure, secondarysubstrate specificitytrypanosoma brucei bruceiudpglucose 4-epimeraseuridine diphosphate galactosebiochemistrystructural biologygeneticsbiophysicscondensed matter physics ??
ID Code:
66398
Deposited By:
Deposited On:
17 Sep 2013 08:08
Refereed?:
Yes
Published?:
Published
Last Modified:
15 Jul 2024 14:12