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#36944394 
2023/03/19
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The crystal structure of Mycobacterium thermoresistibile MurE ligase reveals the binding mode of the substrate m-diaminopimelate.
The cytoplasmatic biosynthesis of the stem peptide from the peptidoglycan in bacteria involves six steps, which have the role of three ATP-dependent Mur ligases that incorporate three consecutive amino acids to a substrate precursor. MurE is the last Mur ligase to incorporate a free amino acid. Although the structure of MurE from Mycobacterium tuberculosis (MtbMurE) was determined at 3.0Å, the binding mode of (meso-Diaminopimelate) m-DAP and the effect of substrate absence is unknown. Herein, we show the structure of MurE from M. thermoresistibile (MthMurE) in complex with ADP and m-DAP at 1.4 Å resolution. The analysis of the structure indicates key conformational changes that the substrate UDP-MurNAc-L-Ala-D-Glu (UAG) and the free amino acid m-DAP cause on the MthMurE conformation. We observed several movements of domains or loop regions that displace their position in order to perform enzymatic catalysis. Since MthMurE has a high similarity to MtbMurE, this enzyme could also guide strategies for structure-based antimicrobial discovery to fight against tuberculosis or other mycobacterial infections. Synopsis Structural characterization of Mycobacterium thermoresistibile MurE at 1.45Å resolution in complex with ADP and m-DAP shows novel conformational changes when compared to other MurE structures in complex with different ligands.Nicolas de Oliveira Rossini, Catharina Dos Santos Silva, Marcio Vinicius Bertacine Dias