4C12

X-ray Crystal Structure of Staphylococcus aureus MurE with UDP-MurNAc- Ala-Glu-Lys and ADP

4C12 の概要

• エントリーDOI: 10.2210/pdb4c12/pdb
• 関連するPDBエントリー: 4C13
• 関連するBIRD辞書のPRD_ID: PRD_002099
• 分子名称: UDP-N-ACETYLMURAMOYL-L-ALANYL-D-GLUTAMATE--L-LYSINE LIGASE, GLYCEROL, Uridine 5'Diphospho N-acetyl muramoyl-L-Alanyl-D-Glutamyl-L-Lysine, ... (6 entities in total)
• 機能のキーワード: ligase
• 由来する生物種: STAPHYLOCOCCUS AUREUS
• 細胞内の位置: Cytoplasm (By similarity): Q2FZP6
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 56950.25

構造登録者

Fulop, V.,Roper, D.I.,Ruane, K.M.,Barreteau, H.,Boniface, A.,Dementin, S.,Blanot, D.,Mengin-Lecreulx, D.,Gobec, S.,Dessen, A.,Dowson, C.G.,Lloyd, A.J. (登録日: 2013-08-09, 公開日: 2013-10-02, 最終更新日: 2023-12-20)

主引用文献

Ruane, K.M.,Lloyd, A.J.,Fulop, V.,Dowson, C.G.,Barreteau, H.,Boniface, A.,Dementin, S.,Blanot, D.,Mengin-Lecreulx, D.,Gobec, S.,Dessen, A.,Roper, D.I.
Specificity Determinants for Lysine Incorporation in Staphylococcus Aureus Peptidoglycan as Revealed by the Structure of a Mure Enzyme Ternary Complex.
J.Biol.Chem., 288:33439-, 2013

PubMed Abstract: Formation of the peptidoglycan stem pentapeptide requires the insertion of both L and D amino acids by the ATP-dependent ligase enzymes MurC, -D, -E, and -F. The stereochemical control of the third position amino acid in the pentapeptide is crucial to maintain the fidelity of later biosynthetic steps contributing to cell morphology, antibiotic resistance, and pathogenesis. Here we determined the x-ray crystal structure of Staphylococcus aureus MurE UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:meso-2,6-diaminopimelate ligase (MurE) (E.C. 6.3.2.7) at 1.8 Å resolution in the presence of ADP and the reaction product, UDP-MurNAc-L-Ala-γ-D-Glu-L-Lys. This structure provides for the first time a molecular understanding of how this Gram-positive enzyme discriminates between L-lysine and D,L-diaminopimelic acid, the predominant amino acid that replaces L-lysine in Gram-negative peptidoglycan. Despite the presence of a consensus sequence previously implicated in the selection of the third position residue in the stem pentapeptide in S. aureus MurE, the structure shows that only part of this sequence is involved in the selection of L-lysine. Instead, other parts of the protein contribute substrate-selecting residues, resulting in a lysine-binding pocket based on charge characteristics. Despite the absolute specificity for L-lysine, S. aureus MurE binds this substrate relatively poorly. In vivo analysis and metabolomic data reveal that this is compensated for by high cytoplasmic L-lysine concentrations. Therefore, both metabolic and structural constraints maintain the structural integrity of the staphylococcal peptidoglycan. This study provides a novel focus for S. aureus-directed antimicrobials based on dual targeting of essential amino acid biogenesis and its linkage to cell wall assembly.

PubMed: 24064214
DOI: 10.1074/JBC.M113.508135

実験手法

X-RAY DIFFRACTION (1.8 Å)