IN SILICO CHARACTERIZATION OF GlmU ANTIGENIC MYCOBACTERIUM TUBERCULOSIS PROTEIN

Tuberculosis (TB) is a disease caused by a bacterium called Mycobacterium tuberculosis. The bacteria usually attack the lungs. Tuberculosis is a global health threat and infecting about one third of the human population. Despite having a variety of anti-tuberculous drugs and availability of effective chemotherapy and Bacille-Calmette –Guerin (BCG) vaccine, tuberculosis remains a leading infectious killer world-wide. This has prompted an urgent need of new drugs and the identification of new drug targets. GlmU is a bifunctional acetyltransferase/uridyltransferase that catalyses the formation of UDP-GlcNAc from GlcN-1-P. UDP-GlcNAc is a substrate for two important biosynthetic pathway: lipopolysaccharide and peptidoglycan synthesis. The glmU protein is essential in Mycobacterium tuberculosis, being required for optimal bacterial growth. Since inhibition of GlmU affects peptidoglycan synthesis which often results in cell lysis, M. tuberculosis GlmU is a potential anti-tuberculosis drug target. The primary protein sequence analysis was done using protparam tool and secondary structure prediction was done using SOPMA. The NTP_transferase domain and IspD domain found in GlmU protein were identified by SMART and its 3D structure prediction was done using modeller. Model quality was analyzed using PROCHECK and showed 91.7% of residues in most favored region in Ramachandran plot. Further the active site residues of bifunctional GlmU proteins were identified from Catalytic Site Atlas (CSA) and catalytic residues were Glu-385 and Arg-19. This in silico sequence and structure analysis is helpful for identification and validation of drug target in Mycobacterium tuberculosis.