ATP-binding mode including a carbamoylated lysine and two Mg(2+) ions, and substrate-binding mode in Acinetobacter baumannii MurF.
Biochem Biophys Res Commun
; 450(2): 1045-50, 2014 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-24978312
ABSTRACT
MurF adds d-Ala-d-Ala dipeptide to UDP-N-acetylmuramyl-l-Ala-γ-d-Glu-m-DAP (or l-Lys) in an ATP-dependent manner, which is the last step in the biosynthesis of monomeric precursor of peptidoglycan. Here we report crystal structures of two MurF-ATP complexes the MurF-ATP complex and the MurF-ATP-UDP complex. The ATP-binding mode revealed by the crystal structure of the MurF-ATP complex confirms the previous biochemical demonstration that a carbamoylated lysine and two Mg(2+) ions are required for enzyme activity of MurF. The UDP-MurF interactions observed in the crystal structure of the MurF-ATP-UDP complex depict the characteristic substrate-binding mode of MurF. The emergence and dissemination of multidrug-resistant Acinetobacter baumannii strains are great threats to public health. Therefore, the structural information on A. baumannii MurF as a validated target for drug discovery will provide a framework to develop antibacterial agents against multidrug-resistant A. baumannii infections as well as to understand the reaction mechanism of MurF.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Sintases
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Difosfato de Uridina
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Carbamatos
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Trifosfato de Adenosina
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Acinetobacter baumannii
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Lisina
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Manganês
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article