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 Mg2+ 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.
|Number of pages
|Biochemical and Biophysical Research Communications
|Published - 25 Jul 2014
Bibliographical noteFunding Information:
This study was supported by the National Research Foundation of Korea Grant NRF-2012R1A2A2A02005978 and the KIOST in-house programs ( PE99212 and PE99263 ).
- Carbamoylated lysine
- Crystal structure
- MurF-ATP complex
- MurF-ATP-UDP complex