3RDR

Structure of the catalytic domain of XlyA

「3HMA」から置き換えられました

3RDR の概要

• エントリーDOI: 10.2210/pdb3rdr/pdb
• 分子名称: N-acetylmuramoyl-L-alanine amidase XlyA, ZINC ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: t7 lysozyme fold, amidase, hydrolase
• 由来する生物種: Bacillus subtilis
• 細胞内の位置: Secreted (Potential): P39800
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17208.83

構造登録者

Low, L.Y.,Liddington, R.C. (登録日: 2011-04-01, 公開日: 2011-08-10, 最終更新日: 2024-02-21)

主引用文献

Low, L.Y.,Yang, C.,Perego, M.,Osterman, A.,Liddington, R.
Role of net charge on catalytic domain and influence of cell wall binding domain on bactericidal activity, specificity, and host range of phage lysins.
J.Biol.Chem., 286:34391-34403, 2011

PubMed Abstract: The recombinant lysins of lytic phages, when applied externally to Gram-positive bacteria, can be efficient bactericidal agents, typically retaining high specificity. Their development as novel antibacterial agents offers many potential advantages over conventional antibiotics. Protein engineering could exploit this potential further by generating novel lysins fit for distinct target populations and environments. However, access to the peptidoglycan layer is controlled by a variety of secondary cell wall polymers, chemical modifications, and (in some cases) S-layers and capsules. Classical lysins require a cell wall-binding domain (CBD) that targets the catalytic domain to the peptidoglycan layer via binding to a secondary cell wall polymer component. The cell walls of Gram-positive bacteria generally have a negative charge, and we noticed a correlation between (positive) charge on the catalytic domain and bacteriolytic activity in the absence of the CBD (nonclassical behavior). We investigated a physical basis for this correlation by comparing the structures and activities of pairs of lysins where the lytic activity of one of each pair was CBD-independent. We found that by engineering a reversal of sign of the net charge of the catalytic domain, we could either eliminate or create CBD dependence. We also provide evidence that the S-layer of Bacillus anthracis acts as a molecular sieve that is chiefly size-dependent, favoring catalytic domains over full-length lysins. Our work suggests a number of facile approaches for fine-tuning lysin activity, either to enhance or reduce specificity/host range and/or bactericidal potential, as required.

PubMed: 21816821
DOI: 10.1074/jbc.M111.244160

実験手法

X-RAY DIFFRACTION (2.2 Å)