Steve Ealick's Research Group

Streptococcus pneumoniae Nicotinamidase

PDB files:

3O90, unliganded

3O91, nicotinaldehyde complex,

3O92, 5-methoxynicotinaldehyde complex

3O93, nicotinoyl-thioester complex

3O94, C136S-nicotinamide complex


Nicotinamidases are salvage enzymes that convert nicotinamide to nicotinic acid. These enzymes are essential for the recycling of nicotinamide into NAD+ in most prokaryotes, most single cell and multicellular eukaryotes, but not in mammals. The significance of these enzymes for nicotinamide salvage and for NAD+ homeostasis has increased interest in nicotinamidases as possible antibiotic targets. Nicotinamidases are also regulators of intracellular nicotinamide concentrations, thereby regulating signaling of downstream NAD+ consuming enzymes, such as the NAD+-dependent deacetylases (sirtuins). We determined the structure of Streptococcus pneumoniae nicotinamidase, both unliganded and in several complexes.

SpNic is an α/β protein in which each protomer is comprised of a six-stranded β-sheet flanked by three helices on one side and four helices on the opposite side.


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SpNic is a homotetramer, consistent with molecular weight estimates determined by size exclusion chromatography.  Each protomer has an active site that is located in a solvent-accessible pocket.

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The active site was probed by the crystallization of several complexes. Data indicate that the native enzyme contains zinc ions and that there is an active site water molecule coordinated to the metal.

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French JB, Cen Y, Sauve AA, and Ealick SE. High Resolution Crystal Structures of Streptococcus pneumoniae Nicotinamidase with Trapped Intermediates Provide Insights into Catalytic Mechanism and Inhibition by Aldehydes. Biochemistry 49:8803-8812 (2010). PubMed

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