4K6T

Crystal structure of Ad37 fiber knob in complex with trivalent sialic acid inhibitor ME0385

4K6T の概要

• エントリーDOI: 10.2210/pdb4k6t/pdb
• 関連するPDBエントリー: 1UXE 3N0I 3QND 4K6U 4K6V 4K6W
• 分子名称: Fiber protein, CALCIUM ION, N-acetyl-alpha-neuraminic acid, ... (11 entities in total)
• 機能のキーワード: adenovirus, fiber knob, protein carbohydrate interaction, sialic acid, carbohydrate mimic, multivalent ligand, viral protein
• 由来する生物種: Human adenovirus 37
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 135298.89

構造登録者

Stehle, T.,Bauer, J. (登録日: 2013-04-16, 公開日: 2014-10-22, 最終更新日: 2024-04-03)

主引用文献

Caraballo, R.,Saleeb, M.,Bauer, J.,Liaci, A.M.,Chandra, N.,Storm, R.J.,Frangsmyr, L.,Qian, W.,Stehle, T.,Arnberg, N.,Elofsson, M.
Triazole linker-based trivalent sialic acid inhibitors of adenovirus type 37 infection of human corneal epithelial cells.
Org.Biomol.Chem., 13:9194-9205, 2015

PubMed Abstract: Adenovirus type 37 (Ad37) is one of the principal agents responsible for epidemic keratoconjunctivitis (EKC), a severe ocular infection that remains without any available treatment. Recently, a trivalent sialic acid derivative (ME0322, Angew. Chem. Int. Ed., 2011, 50, 6519) was shown to function as a highly potent inhibitor of Ad37, efficiently preventing the attachment of the virion to the host cells and subsequent infection. Here, new trivalent sialic acid derivatives were designed, synthesized and their inhibitory properties against Ad37 infection of the human corneal epithelial cells were investigated. In comparison to ME0322, the best compound (17a) was found to be over three orders of magnitude more potent in a cell-attachment assay (IC50 = 1.4 nM) and about 140 times more potent in a cell-infection assay (IC50 = 2.9 nM). X-ray crystallographic analysis demonstrated a trivalent binding mode of all compounds to the Ad37 fiber knob. For the most potent compound ophthalmic toxicity in rabbits was investigated and it was concluded that repeated eye administration did not cause any adverse effects.

PubMed: 26177934
DOI: 10.1039/c5ob01025j

実験手法

X-RAY DIFFRACTION (2 Å)