Crystal structure of dehydratase component HadAB complex of mycobacterial FAS-II pathway

• DOI: 10.1016/j.bbrc.2015.01.119
• Publication Date: 2015-02-03T01:03:22Z
• Authors: Rupam Biswas; Anirudha Dutta; Debajyoti Dutta; Ditipriya Hazra; Deb Ranjan Banerjee; Amit Basak; Amit Kumar Das
• Keywords: Models, Molecular; 0301 basic medicine; Protein Folding; Protein Conformation; Molecular Sequence Data; Mycobacterium tuberculosis; Enzyme Activation; Structure-Activity Relationship; 03 medical and health sciences; Models, Chemical; Multiprotein Complexes; Fatty Acid Synthase, Type II; Computer Simulation; Amino Acid Sequence; Crystallization; Dimerization; Enoyl-CoA Hydratase; Protein Binding; Signal Transduction

Fatty acid biosynthesis type II in mycobacteria delivers the fatty acids required for mycolic acid synthesis. The pathway employs a unique maoC like β-hydroxyacyl-ACP dehydratase HadAB or HadBC heterodimer in the third step of the elongation cycle. Here we report the crystal structure of the HadAB complex determined using a Pb-SIRAS method. Crystal structure aided with enzymatic study establishes the roles of HadA as a scaffolding component and HadB as a catalytic component together indispensable for the activity. The detailed structural analysis of HadAB in combination with MD simulation endorses the spatial orientation of the central hot-dog helix and the dynamic nature of its associated loop in regulation of substrate specificities in dehydratase/hydratase family enzymes.