肺炎克雷伯菌
微生物学
噬菌体
多糖
克雷伯菌
降级(电信)
化学
生物
生物化学
大肠杆菌
基因
电信
计算机科学
作者
Tian-Yun Huang,Zhuoyuan Zhang,Xin Tao,Xinyu Shi,Peng Lin,Dan Liu,Chunyan Ma,Xueting Cai,Wei Lin,Xiaofan Jiang,Peng Luo,Shengxi Wu,Yuan Xie
标识
DOI:10.1016/j.ijbiomac.2024.130917
摘要
Capsule polysaccharide is an important virulence factor of Klebsiella pneumoniae (K. pneumoniae), which protects bacteria against the host immune response. A promising therapeutic approach is using phage-derived depolymerases to degrade the capsular polysaccharide and expose and sensitize the bacteria to the host immune system. Here we determined the cryo-electron microscopy (cryo-EM) structures of a bacteriophage tail-spike protein against K. pneumoniae K64, ORF41 (K64-ORF41) and ORF41 in EDTA condition (K64-ORF41EDTA), at 2.37 Å and 2.50 Å resolution, respectively, for the first time. K64-ORF41 exists as a trimer and each protomer contains a β-helix domain including a right-handed parallel β-sheet helix fold capped at both ends, an insertion domain, and one β-sheet jellyroll domain. Moreover, our structural comparison with other depolymerases of K. pneumoniae suggests that the catalytic residues (Tyr528, His574 and Arg628) are highly conserved although the substrate of capsule polysaccharide is variable. Besides that, we figured out the important residues involved in the substrate binding pocket including Arg405, Tyr526, Trp550 and Phe669. This study establishes the structural and functional basis for the promising phage-derived broad-spectrum activity depolymerase therapeutics and effective CPS-degrading agents for the treatment of carbapenem-resistant K. pneumoniae K64 infections.
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