Crystal structure of UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) from Mycobacterium tuberculosis

Publication date: Available online 5 December 2017 Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics Author(s): Kandasamy Eniyan, Sudhaker Dharavath, Ramachandran Vijayan, Urmi Bajpai, Samudrala Gourinath The biosynthesis of UDP-N-acetylmuramic acid (UDP-MurNAc) by reduction of UDP-N-acetylglucosamine-enolpyruvate (UDP-GlcNAc-EP) in an NADPH and FAD-dependent reaction in bacteria is one of the key steps in peptidoglycan biosynthesis catalyzed by UDP-N-acetylglucosamine-enolpyruvate reductase (MurB). Here, we present the crystal structure of Mycobacterium tuberculosis MurB (MtbMurB) with FAD as the prosthetic group at 2.0Å resolution. There are six molecules in asymmetric unit in the form of dimers. Each protomer can be subdivided into three domains and the prosthetic group, FAD is bound in the active site between domain I and domain II. Comparison of MtbMurB structure with the structures of the Escherichia coli MurB (in complex with UDP-GlcNAc-EP) and Pseudomonas aeruginosa MurB (in complex with NADPH) showed all three structures share similar domain architecture and residues in the active site. The nicotinamide and the enol pyruvyl moieties are well aligned upon superimposition, both positioned in suitable position for hydride transfer to and from FAD. The comparison studies and MD simulations demonstrate that the two lobes of domain-III become more flexible. The substrates (NADPH and UDP-GlcNAc-EP) binding responsible for open conformation of MurB...
Source: Biochimica et Biophysica Acta (BBA) Proteins and Proteomics - Category: Biochemistry Source Type: research