Mycobacterium Tuberculosis Transpeptidase Domain

Tuberculosis (TB) is one of the major human respiratory diseases which is caused by Mycobacterium Tuberculosis. The infection of M. tuberculosis causes a large area of necrosis of pulmonary tissue, which results in significant breathing difficulties. TB is also known to be a major causing agent for chronic obstructive pulmonary disease (COPD). Nowadays, TB proposes a significant problem in antibiotic resistance, traditional antibiotics gradually become less and less effective towards the antibiotic-resistant strain of M. tuberculosis. In order to develop a novel antibiotic, further research has led us into the mechanism of how known antibiotic acts on M. tuberculosis. A new therapeutic approach is taken by investigating the penicillium binding site PonA1.

Function

Two types of Penicillin-binding proteins (PBPs) can be found in M. tuberculosis, which is PonA1 and PonA2. PonA1 is responsible for the integrity of the poly peptidoglycans, which also regulates the cell wall in the growth of the cell cycle. From research suggest that the function of PBPs PonA2 possess the ability to sense cell cycle and responsible for protein-carbohydrates interactions.

When the ß-lactams bind to the PBPs, it induces the degradation of the cell wall by inhibits the activity of transpeptidase.

Disease

TB results from an infection of M. tuberculosis. the bacteria can be transmitted in airborne droplets from sneezing or coughing. the major symptom of TB is presented as pulmonary infection, however, M. tuberculosis can infect any part of the body.

Structural highlights

PonA1 binding site without ligand. Residues involved in the binding of penicillin V is highlighted in gold. The remaining framework is reduced as simple strands for better contrast.

Penicillin V binds to the transpeptidase domain of this protein. In this view penicillin V is shown as ball and stick, with the carbon atoms in red. This chains that is involved in hydrogen bonding with penicillin V are shown in gold.

BlaC redo

Medical Importance

By understanding the mechanism from the binding of penicillin V to TB Transpeptidase domain, may allow us to develop novel inhibitors for treating the disease.