7BFY

Structure of the apo form of the N terminal domain of Bc2L-C lectin (1-131)

7BFY の概要

• エントリーDOI: 10.2210/pdb7bfy/pdb
• 分子名称: Lectin (2 entities in total)
• 機能のキーワード: lectins, drug resistance, glycomimetics, anti-adhesive therapy, drug design, fragment-based screening, sugar binding protein
• 由来する生物種: Burkholderia cenocepacia J2315
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13744.66

構造登録者

Lal, K.,Bermeo, R.,Imberty, A.,Varrot, A. (登録日: 2021-01-05, 公開日: 2021-04-07, 最終更新日: 2024-01-31)

主引用文献

Lal, K.,Bermeo, R.,Cramer, J.,Vasile, F.,Ernst, B.,Imberty, A.,Bernardi, A.,Varrot, A.,Belvisi, L.
Prediction and Validation of a Druggable Site on Virulence Factor of Drug Resistant Burkholderia cenocepacia*.
Chemistry, 27:10341-10348, 2021

PubMed Abstract: Burkholderia cenocepacia is an opportunistic Gram-negative bacterium that causes infections in patients suffering from chronic granulomatous diseases and cystic fibrosis. It displays significant morbidity and mortality due to extreme resistance to almost all clinically useful antibiotics. The bacterial lectin BC2L-C expressed in B. cenocepacia is an interesting drug target involved in bacterial adhesion and subsequent deadly infection to the host. We solved the first high resolution crystal structure of the apo form of the lectin N-terminal domain (BC2L-C-nt) and compared it with the ones complexed with carbohydrate ligands. Virtual screening of a small fragment library identified potential hits predicted to bind in the vicinity of the fucose binding site. A series of biophysical techniques and X-ray crystallographic screening were employed to validate the interaction of the hits with the protein domain. The X-ray structure of BC2L-C-nt complexed with one of the identified active fragments confirmed the ability of the site computationally identified to host drug-like fragments. The fragment affinity could be determined by titration microcalorimetry. These structure-based strategies further provide an opportunity to elaborate the fragments into high affinity anti-adhesive glycomimetics, as therapeutic agents against B. cenocepacia.

PubMed: 33769626
DOI: 10.1002/chem.202100252

実験手法

X-RAY DIFFRACTION (1.5 Å)