Structural and related studies on Mycobacterium tuberculosis pantothenate kinase

Abstract

Pantothenate kinase (PanK) is a ubiquitous and essential enzyme that catalyses the first step in the universal Coenzyme A (CoA) biosynthetic pathway. In this step pantothenate is converted to phosphopantothentate, which subsequently forms CoA in four enzymatic steps. Three types of PanKs have been identified in bacteria, with variations in distribution, mechanism of regulation, cofactor requirement and affinity for substrates. As part of a major programme on mycobacterial proteins in our laboratory, studies on type I PanK from Mycobacterium tuberculosis (MtPanK) have been carried out previously. This investigation involved, apart from biochemical studies, structure determination of twenty-one independent crystals of binary and ternary complexes of MtPanK involving CoA, the ATP analogue AMPPCP, the GTP analogue GMPPCP, ADP, GDP, pantothenate, phosphopantothenate, citrate, pantothenol and nonyl pantothenamide. Analysis of these structures brought out the robustness of the mycobacterial PanK when compared to its E. coli homologue... newline