3lu1
Crystal Structure Analysis of WbgU: a UDP-GalNAc 4-epimerase
Structural highlights
FunctionGNE_PLESH Catalyzes the epimerization of UDP-N-acetylglucosamine (UDP-GlcNAc) to UDP-N-acetylgalactosamine (UDP-GalNAc). Has very low epimerase activity with UDP-Glc and UDP-Gal. Plays a role in the biosynthesis of 2-acetamino-2-deoxy-L-altruronic acid, a building block of the O-antigen in bacterial lipopolysaccharide (LPS).[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedUDP-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. Altered architecture of substrate binding region defines the unique specificity of UDP-GalNAc 4-epimerases.,Bhatt VS, Guo CY, Guan W, Zhao G, Yi W, Liu ZJ, Wang PG Protein Sci. 2011 May;20(5):856-66. doi: 10.1002/pro.611. Epub 2011 Apr 5. PMID:21384454[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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