4ZRM: Crystal Structure Of Udp-glucose 4-epimerase (tm0509) From Hyperthermophilic Eubacterium Thermotoga Maritima

Citation:
Abstract
UDP-galactose 4-epimerase (GalE) catalyzes the interconversion of UDP-glucose (UDP-Glc) and UDP-galactose (UDP-Gal), which is a pivotal step in the Leloir pathway for d-galactose metabolism. Although GalE is widely distributed in prokaryotes and eukaryotes, little information is available regarding hyperthermophilic GalE. We overexpressed the TM0509 gene, encoding a putative GalE from Thermotoga maritima (TMGalE), in Escherichia coli and characterized the encoded protein. To further investigate the molecular basis of this enzyme's catalytic function, we determined the crystal structures of TMGalE and TMGalE bound to UDP-Glc at resolutions of 1.9 A and 2.0 A, respectively. The enzyme was determined to be a homodimer with a molecular mass of 70 kDa. The enzyme could reversibly catalyze the epimerization of UDP-GalNAc/UDP-GlcNAc as well as UDP-Gal/UDP-Glc at elevated temperatures, with an apparent optimal temperature and pH of 80 degrees C and 7.0, respectively. Our data showed that TM0509 is a UDP-galactosugar 4-epimerase involved in d-galactose metabolism; consequently, this study provides the first detailed characterization of a hyperthermophilic GalE. Moreover, the promiscuous substrate specificity of TMGalE, which is more similar to human GalE than E. coli GalE, supports the notion that TMGalE might exhibit the earliest form of sugar-epimerizing enzymes in the evolution of galactose metabolism.
PDB ID: 4ZRMDownload
MMDB ID: 132660
PDB Deposition Date: 2015/5/12
Updated in MMDB: 2015/11
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Similar Structures:
Biological Unit for 4ZRM: dimeric; determined by author and by software (PISA)
Molecular Components in 4ZRM
Label Count Molecule
Proteins (2 molecules)
2
Udp-glucose 4-epimerase
Molecule annotation
Chemicals (5 molecules)
1
2
2
3
* Click molecule labels to explore molecular sequence information.

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