4EHX

Crystal structure of LpxK from Aquifex aeolicus at 1.9 angstrom resolution

4EHX の概要

• エントリーDOI: 10.2210/pdb4ehx/pdb
• 関連するPDBエントリー: 4EHW 4EHY
• 分子名称: Tetraacyldisaccharide 4'-kinase, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: membrane protein, kinase, lipid a, p-loop, p-loop containing nucleoside triphosphate hydrolase, disaccharide-1-phosphate 4'-kinase, membrane, transferase, lipid metabolism, tetraacyldisaccharide 4'-kinase
• 由来する生物種: Aquifex aeolicus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37809.14

構造登録者

Emptage, R.P.,Daughtry, K.D.,Pemble IV, C.W.,Raetz, C.R.H. (登録日: 2012-04-04, 公開日: 2012-08-29, 最終更新日: 2023-09-13)

主引用文献

Emptage, R.P.,Daughtry, K.D.,Pemble, C.W.,Raetz, C.R.
Crystal structure of LpxK, the 4'-kinase of lipid A biosynthesis and atypical P-loop kinase functioning at the membrane interface.
Proc.Natl.Acad.Sci.USA, 109:12956-12961, 2012

PubMed 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.

PubMed: 22826246
DOI: 10.1073/pnas.1206072109

実験手法

X-RAY DIFFRACTION (1.9 Å)