title: ATP-binding mode including a carbamoylated lysine and two Mg(2+) ions, and substrate-binding mode in Acinetobacter baumannii MurF.
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.
authors: Marine Biotechnology Research Division, Korea Institute of Ocean Science and Technology, Ansan 426-744, Republic of Korea; Department of Convergence Study on the Ocean Science and Technology, Ocean Science and Technology School, Pusan 606-791, Republic of Korea; Department of Marine Biotechnology, Korea University of Science and Technology, Daejeon 305-333, Republic of Korea. Electronic address: chajung@kiost.ac.
authors: Sun-Shin
authors: SS
authors: Cha
authors: Marine Biotechnology Research Division, Korea Institute of Ocean Science and Technology, Ansan 426-744, Republic of Korea.
authors: Young Jun
authors: YJ
authors: An
authors: Marine Biotechnology Research Division, Korea Institute of Ocean Science and Technology, Ansan 426-744, Republic of Korea.
authors: Chang-Sook
authors: CS
authors: Jeong
authors: Department of Microbiology and Immunology, Chonbuk National University Medical School, Jeonju 561-756, Republic of Korea.
authors: Jeong Hee
authors: JH
authors: Yu
authors: Department of Microbiology and Immunology, Chonbuk National University Medical School, Jeonju 561-756, Republic of Korea; Institute for Medical Science, Chonbuk National University Medical School, Jeonju 561-756, Republic of Korea. Electronic address: kmin@jbnu.ac.kr.
authors: Kyung Min
authors: KM
authors: Chung
mesh_terms: D040981:Acinetobacter baumannii / Q000201:enzymology*; D000255:Adenosine Triphosphate / Q000737:chemistry*; D002219:Carbamates / Q000737:chemistry*; D002413:Cations, Divalent; D018360:Crystallography, X-Ray; D008239:Lysine / Q000737:chemistry*; D008345:Manganese / Q000737:chemistry*; D008958:Models, Molecular; D010453:Peptide Synthases / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D014530:Uridine Diphosphate / Q000737:chemistry*
chemical_list: D002219:Carbamates; D002413:Cations, Divalent; D008345:Manganese; D014530:Uridine Diphosphate; D000255:Adenosine Triphosphate; D010453:Peptide Synthases; C060628:UDP-N-acetylmuramoylalanyl-D-glutamyllysine-D-alanyl-D-alanine ligase; D008239:Lysine
keywords: Carbamoylated lysine; Crystal structure; Magnesium; MurF–ATP complex; MurF–ATP–UDP complex