3OJL

Native structure of the UDP-N-acetyl-mannosamine dehydrogenase Cap5O from Staphylococcus aureus

Summary for 3OJL

• Entry DOI: 10.2210/pdb3ojl/pdb
• Related: 3OJO
• Descriptor: Cap5O, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• Functional Keywords: rossmann fold, binary complex, cofactor nad, dimer, oxidoreduction, oxidoreductase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 97674.33

Authors

Nessler, S.,Gruszczyk, J.,Olivares-Illana, V.,Meyer, P.,Morera, S.,Grangeasse, C.,Fleurie, A. (deposition date: 2010-08-23, release date: 2011-03-23, Last modification date: 2024-10-30)

Primary citation

Gruszczyk, J.,Fleurie, A.,Olivares-Illana, V.,Bechet, E.,Zanella-Cleon, I.,Morera, S.,Meyer, P.,Pompidor, G.,Kahn, R.,Grangeasse, C.,Nessler, S.
Structure Analysis of the Staphylococcus aureus UDP-N-acetyl-mannosamine Dehydrogenase Cap5O Involved in Capsular Polysaccharide Biosynthesis.
J.Biol.Chem., 286:17112-17121, 2011

PubMed Abstract: Bacterial UDP-sugar dehydrogenases are part of the biosynthesis pathway of extracellular polysaccharides. These compounds act as important virulence factors by protecting the cell from opsonophagocytosis and complement-mediated killing. In Staphylococcus aureus, the protein Cap5O catalyzes the oxidation of UDP-N-acetyl-mannosamine to UDP-N-acetyl-mannosaminuronic acid. Cap5O is crucial for the production of serotype 5 capsular polysaccharide that prevents the interaction of bacteria with both phagocytic and nonphagocytic eukaryotic cells. However, details of its catalytic mechanism remain unknown. We thus crystallized Cap5O and solved the first structure of an UDP-N-acetyl-mannosamine dehydrogenase. This study revealed that the catalytic cysteine makes a disulfide bond that has never been observed in other structurally characterized members of the NDP-sugar dehydrogenase family. Biochemical and mutagenesis experiments demonstrated that the formation of this disulfide bridge regulates the activity of Cap5O. We also identified two arginine residues essential for Cap5O activity. Previous data suggested that Cap5O is activated by tyrosine phosphorylation, so we characterized the phosphorylation site and examined the underlying regulatory mechanism.

PubMed: 21454499
DOI: 10.1074/jbc.M110.216002

Experimental method

X-RAY DIFFRACTION (2.8 Å)