A structural and functional perspective on the enzymes of Mycobacterium tuberculosis involved in the L-rhamnose biosynthesis pathway

Abstract

Tuberculosis is one of the leading causes of death from bacterial infections. The multi-drug resistant strain has warranted the development of new drug molecules which can inhibit the growth of Mycobacterium tuberculosis (M.tb). Most of the known drugs inhibit the enzymes in the cell wall biosynthesis pathway. One such pathway is L-rhamnose, which involves four druggable enzymes RmlA, B, C and D. The 3D structure analyses of these protein models (RmlA, B and D) and crystal structure (RmlC) has been carried out. Multiple sequence alignments of homologs from distant species of 32 taxa and analyses of available structures were performed in order to study the conservation of sequence and structural motifs, and catalytically important residues. Based on these results and reported mechanism in other organisms, we have predicted putative catalytic mechanism of M.tb enzymes involved in the L-rhamnose biosynthesis pathway.