The crystal structure of Mycobacterium thermoresistibile MurE ligase reveals the binding mode of the substrate m-diaminopimelate.
J Struct Biol
; 215(2): 107957, 2023 06.
Article
em En
| MEDLINE
| ID: mdl-36944394
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 3.0 Å, 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Sintases
/
Mycobacterium tuberculosis
Idioma:
En
Revista:
J Struct Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos