4ehy | pdb_00004ehy

Crystal structure of LpxK from Aquifex aeolicus in complex with ADP/Mg2+ at 2.2 angstrom resolution

spinqualitylabelsall models 4ehy, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ehy is a 1 chain structure with sequence from Aquae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, CL, GOL, MG Related: 4ehw, 4ehx Gene: aq_1656, lpxK (AQUAE) Activity: Tetraacyldisaccharide 4'-kinase, with EC number 2.7.1.130 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [LPXK_AQUAE] Transfers the gamma-phosphate of ATP to the 4'-position of a tetraacyldisaccharide 1-phosphate intermediate (termed DS-1-P) to form tetraacyldisaccharide 1,4'-bis-phosphate (lipid IVA) (By similarity). Publication Abstract from PubMed In Gram-negative bacteria, the hydrophobic anchor of the outer membrane lipopolysaccharide is lipid A, a saccharolipid that plays key roles in both viability and pathogenicity of these organisms. The tetraacyldisaccharide 4'-kinase (LpxK) of the diverse P-loop-containing nucleoside triphosphate hydrolase superfamily catalyzes the sixth step in the biosynthetic pathway of lipid A, and is the only known P-loop kinase to act upon a lipid substrate at the membrane. Here, we report the crystal structures of apo- and ADP/Mg(2+)-bound forms of Aquifex aeolicus LpxK to a resolution of 1.9 A and 2.2 A, respectively. LpxK consists of two alpha/beta/alpha sandwich domains connected by a two-stranded beta-sheet linker. The N-terminal domain, which has most structural homology to other family members, is responsible for catalysis at the P-loop and positioning of the disaccharide-1-phosphate substrate for phosphoryl transfer on the inner membrane. The smaller C-terminal domain, a substructure unique to LpxK, helps bind the nucleotide substrate and Mg(2+) cation using a 25 degrees hinge motion about its base. Activity was severely reduced in alanine point mutants of conserved residues D138 and D139, which are not directly involved in ADP or Mg(2+) binding in our structures, indicating possible roles in phosphoryl acceptor positioning or catalysis. Combined structural and kinetic studies have led to an increased understanding of the enzymatic mechanism of LpxK and provided the framework for structure-based antimicrobial design. Crystal structure of LpxK, the 4'-kinase of lipid A biosynthesis and atypical P-loop kinase functioning at the membrane interface.,Emptage RP, Daughtry KD, Pemble CW 4th, Raetz CR Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):12956-61. Epub 2012 Jul 23. PMID:22826246 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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