2CNB

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

Summary for 2CNB

• Entry DOI: 10.2210/pdb2cnb/pdb
• Related: 1GY8
• Descriptor: UDP-GALACTOSE-4-EPIMERASE, URIDINE-5'-DIPHOSPHATE-4-DEOXY-4-FLUORO-ALPHA-D-GALACTOSE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: epimerase, short-chain dehydrogenase/reductase, udp-galactose-4- epimerase, nad, isomerase, trypanosoma brucei, udp-4-deoxy- 4-fluoro-alpha-d-galactose
• Biological source: TRYPANOSOMA BRUCEI
• Total number of polymer chains: 4
• Total formula weight: 180153.06

Authors

Alphey, M.S.,Ferguson, M.A.J.,Hunter, W.N. (deposition date: 2006-05-18, release date: 2006-06-12, Last modification date: 2024-05-08)

Primary citation

Alphey, M.S.,Burton, A.,Urbaniak, M.,Boons, G.J.,Ferguson, M.A.J.,Hunter, W.N.
Trypanosoma Brucei Udp-Galactose-4-Epimerase in Ternary Complex with Nad+ and the Substrate Analogue Udp-4-Deoxy-4-Fluoro-Alpha-D-Galactose
Acta Crystallogr.,Sect.F, 62:829-, 2006

PubMed 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.

PubMed: 16946458
DOI: 10.1107/S1744309106028740

Experimental method

X-RAY DIFFRACTION (2.7 Å)