4K6V: Crystal structure of Ad37 fiber knob in complex with trivalent sialic acid inhibitor ME0407

Citation:
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.
PDB ID: 4K6VDownload
MMDB ID: 124016
PDB Deposition Date: 2013/4/16
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.5  Å
Source Organism:
Similar Structures:
Biological Unit for 4K6V: trimeric; determined by author and by software (PISA)
Molecular Components in 4K6V
Label Count Molecule
Proteins (3 molecules)
3
Fiber Protein
Molecule annotation
Chemicals (15 molecules)
1
3
2
3
3
1
4
4
5
3
6
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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