7DC0

Crystal structure of glycan-free Pseudomonas taiwanensis lectin

7DC0 の概要

• エントリーDOI: 10.2210/pdb7dc0/pdb
• 分子名称: Lectin, SULFATE ION (3 entities in total)
• 機能のキーワード: beta barrel, antiviral lectin, carbohydrate binding, sugar binding protein
• 由来する生物種: Pseudomonas taiwanensis DSM 21245
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28969.55

構造登録者

Oda, K.,Matoba, Y. (登録日: 2020-10-23, 公開日: 2021-04-28, 最終更新日: 2023-11-29)

主引用文献

Matoba, Y.,Sato, Y.,Oda, K.,Hatori, Y.,Morimoto, K.
Lectins engineered to favor a glycan-binding conformation have enhanced antiviral activity.
J.Biol.Chem., 296:100698-100698, 2021

PubMed Abstract: Homologues of the Oscillatoria agardhii agglutinin (OAA) lectins contain a sequence repeat of ∼66 amino acids, with the number of tandem repeats varying across family members. OAA homologues bind high-mannose glycans on viral surface proteins, thereby interfering with viral entry into host cells. As such, OAA homologues have potential utility as antiviral agents, but a more detailed understanding of their structure-function relationships would enable us to develop improved constructs. Here, we determined the X-ray crystal structure of free and glycan-bound forms of Pseudomonas taiwanensis lectin (PTL), an OAA-family lectin consisting of two tandem repeats. Like other OAA-family lectins, PTL exhibited a β-barrel-like structure with two symmetrically positioned glycan-binding sites at the opposite ends of the barrel. Upon glycan binding, the conformation of PTL undergoes a more significant change than expected from previous OAA structural analysis. Moreover, the electron density of the bound glycans suggested that the binding affinities are different at the two binding sites. Next, based on analysis of these structures, we used site-specific mutagenesis to create PTL constructs expected to increase the population with a conformation suitable for glycan binding. The engineered PTLs were examined for their antiviral activity against the influenza virus. Interestingly, some exhibited stronger activity compared with that of the parent PTL. We propose that our approach is effective for the generation of potential microbicides with enhanced antiviral activity.

PubMed: 33895142
DOI: 10.1016/j.jbc.2021.100698

実験手法

X-RAY DIFFRACTION (1.88 Å)