ArticleProceedings of the National Academy of Sciences of the United States of America2012
Crystal structure of LpxK, the 4'-kinase of lipid A biosynthesis and atypical P-loop kinase functioning at the membrane interface.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 19 citations in OpenAlex.
- Structure and function of Salmonella inner membrane.Archives of microbiology · 2026Review
- An energy-conserving reaction in amino acid metabolism catalyzed by arginine synthetase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural characterization of a novel cyclic 2,3-diphosphoglycerate synthetase involved in extremolyte production in the archaeonFrontiers in microbiology · 2023Article
- Pharmacoinformatics approaches to identify potential hits against tetraacyldisaccharide 4'-kinase (LpxK) ofRSC advances · 2020Article
- Monotopic Membrane Proteins Join the Fold.Trends in biochemical sciences · 2019Review
- Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli.Nature communications · 2018Article
- Current Progress in the Structural and Biochemical Characterization of Proteins Involved in the Assembly of Lipopolysaccharide.International journal of microbiology · 2018Review
- Structure, inhibition, and regulation of essential lipid A enzymes.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
- A two-helix motif positions the lysophosphatidic acid acyltransferase active site for catalysis within the membrane bilayer.Nature structural & molecular biology · 2017Article
- Unique lipid anchor attaches Vi antigen capsule to the surface of Salmonella enterica serovar Typhi.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Kdo2 -lipid A: structural diversity and impact on immunopharmacology.Biological reviews of the Cambridge Philosophical Society · 2015Review
- Structural basis of lipid binding for the membrane-embedded tetraacyldisaccharide-1-phosphate 4'-kinase LpxK.The Journal of biological chemistry · 2014Article
- Article
- A divergent Pseudomonas aeruginosa palmitoyltransferase essential for cystic fibrosis-specific lipid A.Molecular microbiology · 2014Article
- Mechanistic characterization of the tetraacyldisaccharide-1-phosphate 4'-kinase LpxK involved in lipid A biosynthesis.Biochemistry · 2013Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
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 Å and 2.2 Å, respectively. LpxK consists of two α/β/α sandwich domains connected by a two-stranded β-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° 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.
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