Abstract

TARGET ENZYMES IN MYCOBACTERIUM TUBERCULOSIS

Mrunmayee Toraskar* and Pravin khude

Abstract

When antibiotic loses its ability to effectively control or kill bacterial growth, it leads to antibiotics resistance. Bacteria acquire resistance in various possible ways; by genetic mutation and by acquiring resistance from another bacterium with existing resistant genes etc. Recently, almost 80% strains of Escherichia coli have become resistant to ampicillin, which has been used to treat E.coli infection since 1960’s. Same is for the Staphylococcus aureus strains causing infection which have become resistant to methicillin. Mycobacterium tuberculosis (M.tb) which has become multi-drug resistant in 1990’s, is the most dangerous among the drug resistant bacteria. For this reason, searching for new target enzyme is the current objective. Catalyzing enzyme malate synthase and isocitratelyase helps escape two CO2 steps in kerb cycle, taking part in glyoxylate shunt leading to formation of malate and acetyl CoA as a net product. β-Carbonic anhydrases (β-CAs) belonging to family of Carbonic anhydrase, present in bacteria and plant kingdom plays a important role through interconversion between carbon dioxide and bicarbonate. β-CAs expressed in M. Tb which acts as target enzyme for anti-tb agents, may help in design of new anti-tb agents. Another enzyme target is β-hydroxy acyl dehydratase (HadAB) which is the catalyzing enzyme in FAS-II reaction for fatty acid synthesis. Conserved gene HadA, HadB and HadC, in their combined form of HadAB and/or HadBC heterodimer is involved in third step reaction of FAS-II. Thorough understanding of structural information of enzyme target can help synthesize new anti-bacterial drugs which may inhibit growth of bacteria and their activity.

Keywords: Malate synthase, Isocitratlyase, ?-carbonic anhydrase, and ?-hydroxy acyl dehydratase.