3BEO

A Structural Basis for the allosteric regulation of non-hydrolyzing UDP-GlcNAc 2-epimerases

Summary for 3BEO

• Entry DOI: 10.2210/pdb3beo/pdb
• Descriptor: UDP-N-acetylglucosamine 2-epimerase, URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE, URIDINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: epimerase, udp-glcnac, allosteric, regulation, isomerase
• Biological source: Bacillus anthracis
• Total number of polymer chains: 2
• Total formula weight: 86111.02

Authors

Velloso, L.M.,Bhaskaran, S.S.,Schuch, R.,Fischetti, V.A.,Stebbins, C.E. (deposition date: 2007-11-19, release date: 2008-02-19, Last modification date: 2024-02-21)

Primary citation

Velloso, L.M.,Bhaskaran, S.S.,Schuch, R.,Fischetti, V.A.,Stebbins, C.E.
A structural basis for the allosteric regulation of non-hydrolysing UDP-GlcNAc 2-epimerases.
Embo Rep., 9:199-205, 2008

PubMed Abstract: The non-hydrolysing bacterial UDP-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase) catalyses the conversion of UDP-GlcNAc into UDP-N-acetylmannosamine, an intermediate in the biosynthesis of several cell-surface polysaccharides. This enzyme is allosterically regulated by its substrate UDP-GlcNAc. The structure of the ternary complex between the Bacillus anthracis UDP-GlcNAc 2-epimerase, its substrate UDP-GlcNAc and the reaction intermediate UDP, showed direct interactions between UDP and its substrate, and between the complex and highly conserved enzyme residues, identifying the allosteric site of the enzyme. The binding of UDP-GlcNAc is associated with conformational changes in the active site of the enzyme. Kinetic data and mutagenesis of the highly conserved UDP-GlcNAc-interacting residues confirm their importance in the substrate binding and catalysis of the enzyme. This constitutes the first example to our knowledge, of an enzymatic allosteric activation by direct interaction between the substrate and the allosteric activator.

PubMed: 18188181
DOI: 10.1038/sj.embor.7401154

Experimental method

X-RAY DIFFRACTION (1.7 Å)