3LU1

Crystal Structure Analysis of WbgU: a UDP-GalNAc 4-epimerase

Summary for 3LU1

• Entry DOI: 10.2210/pdb3lu1/pdb
• Descriptor: WbgU, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, URIDINE-DIPHOSPHATE-N-ACETYLGALACTOSAMINE, ... (7 entities in total)
• Functional Keywords: rossmann fold, epimerase, lipopolysaccharide, glycan, nadh, udp-glcnac, isomerase
• Biological source: Plesiomonas shigelloides
• Total number of polymer chains: 4
• Total formula weight: 169455.86

Authors

Bhatt, V.S.,Guo, C.Y.,Zhao, G.,Yi, W.,Liu, Z.J.,Wang, P.G. (deposition date: 2010-02-16, release date: 2010-07-21, Last modification date: 2023-09-06)

Primary citation

Bhatt, V.S.,Guo, C.Y.,Guan, W.,Zhao, G.,Yi, W.,Liu, Z.J.,Wang, P.G.
Altered architecture of substrate binding region defines the unique specificity of UDP-GalNAc 4-epimerases.
Protein Sci., 20:856-866, 2011

PubMed Abstract: UDP-hexose 4-epimerases play a pivotal role in lipopolysaccharide (LPS) biosynthesis and Leloir pathway. These epimerases are classified into three groups based on whether they recognize nonacetylated UDP-hexoses (Group 1), both N-acetylated and nonacetylated UDP-hexoses (Group 2) or only N-acetylated UDP-hexoses (Group 3). Although the catalysis has been investigated extensively, yet a definitive model rationalizing the substrate specificity of all the three groups on a common platform is largely lacking. In this work, we present the crystal structure of WbgU, a novel UDP-hexose 4-epimerase that belongs to the Group 3. WbgU is involved in biosynthetic pathway of the unusual glycan 2-deoxy-L-altruronic acid that is found in the LPS of the pathogen Pleisomonas shigelloides. A model that defines its substrate specificity is proposed on the basis of the active site architecture. Representatives from all the three groups are then compared to rationalize their substrate specificity. This investigation reveals that the Group 3 active site architecture is markedly different from the "conserved scaffold" of the Group 1 and the Group 2 epimerases and highlights the interactions potentially responsible for the origin of specificity of the Group 3 epimerases toward N-acetylated hexoses. This study provides a platform for further engineering of the UDP-hexose 4-epimerases, leads to a deeper understanding of the LPS biosynthesis and carbohydrate recognition by proteins. It may also have implications in development of novel antibiotics and more economic synthesis of UDP-GalNAc and downstream products such as carbohydrate based vaccines.

PubMed: 21384454
DOI: 10.1002/pro.611

Experimental method

X-RAY DIFFRACTION (2.5 Å)