Title

Molecular characterization of the Borrelia burgdorferi in vivo-essential protein PncA

Authors

Authors

M. W. Jewett; S. Jain; A. K. Linowski; A. Sarkar;P. A. Rosa

Comments

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Abbreviated Journal Title

Microbiology-(UK)

Keywords

LYME-DISEASE SPIROCHETE; LIFE-SPAN EXTENSION; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; NICOTINAMIDASE PNCA; CALORIE RESTRICTION; INITIATION CODON; INFECTIOUS CYCLE; GENE; IDENTIFICATION; Microbiology

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 Borrelia burgdorferi, 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 in vivo importance of PncA, the current annotation for the pncA 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 B. burgdorferi PncA. Our data demonstrate that the PncA protein is 24 aa longer than the currently annotated sequence and that pncA 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 in vivo-essential protein.

Journal Title

Microbiology-Sgm

Volume

157

Publication Date

1-1-2011

Document Type

Article

Language

English

First Page

2831

Last Page

2840

WOS Identifier

WOS:000296177300009

ISSN

1350-0872

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