The Pyridoxal-5′-Phosphate-Dependent Enzymes of Mycobacterium tuberculosis

Enzymes that depend on the cofactor pyridoxal 5 '-phosphate (PLP) catalyze a remarkable variety of biochemical reactions in all organisms. In particular, the genome of Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), encodes 45 bona fide PLP-dependent enzymes plus a few related proteins that presumably do not have enzymic function. The large majority of the 45 enzymes have been characterized in terms of catalytic activity and structure. Several of them have been shown to be central to the bacterium's survival and pathogenicity, while some of these enzymes are targets of an extant drug (d-cycloserine). Herein, the annotated catalog of the PLP-dependent enzymes in M. tuberculosis is presented and analyzed with three main goals in mind. The first will be to assess the specific aspects of mycobacterial metabolism that rely most on PLP-dependent enzymes. A second goal will be to signal those enzymes whose function is still uncertain and whose functional characterization may help to further understand the biology of M. tuberculosis. Finally, we will examine the potential and limitations of targeting the PLP-dependent enzymes for the development of new antimycobacterial drugs.