title: Crystal structure of dehydratase component HadAB complex of mycobacterial FAS-II pathway.
abstract: 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.
authors: Department of Biotechnology, Indian Institute of Technology, Kharagpur, Kharagpur 721302, India.
authors: Rupam
authors: R
authors: Biswas
authors: Department of Biotechnology, Indian Institute of Technology, Kharagpur, Kharagpur 721302, India.
authors: Anirudha
authors: A
authors: Dutta
authors: Department of Biotechnology, Indian Institute of Technology, Kharagpur, Kharagpur 721302, India.
authors: Debajyoti
authors: D
authors: Dutta
authors: Department of Biotechnology, Indian Institute of Technology, Kharagpur, Kharagpur 721302, India.
authors: Ditipriya
authors: D
authors: Hazra
authors: Department of Chemistry, Indian Institute of Technology, Kharagpur, Kharagpur 721302, India.
authors: Deb Ranjan
authors: DR
authors: Banerjee
authors: Department of Chemistry, Indian Institute of Technology, Kharagpur, Kharagpur 721302, India.
authors: Amit
authors: A
authors: Basak
authors: Department of Biotechnology, Indian Institute of Technology, Kharagpur, Kharagpur 721302, India. Electronic address: amitk@hijli.iitkgp.ernet.in.
authors: Amit Kumar
authors: AK
authors: Das
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D003460:Crystallization; D019281:Dimerization; D004746:Enoyl-CoA Hydratase / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D004789:Enzyme Activation; D054889:Fatty Acid Synthase, Type II / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000201:enzymology*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D046912:Multiprotein Complexes; D004746:Enoyl-CoA Hydratase; D054889:Fatty Acid Synthase, Type II
keywords: Dehydratase; Double hot-dog fold; Mycobacterium tuberculosis; Mycolic acid