1887

Abstract

The conversion of nicotinamide to nicotinic acid by nicotinamidase enzymes is a critical step in maintaining NAD homeostasis and contributes to numerous important biological processes in diverse organisms. In , the nicotinamidase enzyme, PncA, is required for spirochaete survival throughout the infectious cycle. Mammals lack nicotinamidases and therefore PncA may serve as a therapeutic target for Lyme disease. Contrary to the importance of PncA, the current annotation for the ORF suggests that the encoded protein may be inactive due to the absence of an N-terminal aspartic acid residue that is a conserved member of the catalytic triad of characterized PncA proteins. Herein, we have used genetic and biochemical strategies to determine the N-terminal sequence of PncA. Our data demonstrate that the PncA protein is 24 aa longer than the currently annotated sequence and that translation is initiated from the rare, non-canonical initiation codon AUU. These findings are an important first step in understanding the catalytic function of this -essential protein.

Funding
This study was supported by the:
  • NIH, NIAID (Award 5K22AI081730)
  • Intramural Research Program of the NIH, NIAID
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2011-10-01
2024-04-20
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