PDBsum entry 4xqa

Viral protein

PDB id: 4xqa

Contents

Protein chains

184 a.a.

Ligands

ACT ×4

423

Metals

_ZN ×3

Waters ×540

PDB id:

4xqa

Name:

Viral protein

Title:

Crystal structure of ad37 fiber knob in complex with trivalent sialic acid inhibitor me0462

Structure:

Fiber. Chain: a, b, c. Fragment: unp residues 177-365. Synonym: fiber protein. Engineered: yes. Other_details: fragment: fiber knob

Source:

Human adenovirus 37. Organism_taxid: 52275. Gene: l5. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.41Å R-factor: 0.145 R-free: 0.172

Authors:

T.Stehle,A.M.Liaci

Key ref:

R.Caraballo et al. (2015). Triazole linker-based trivalent sialic acid inhibitors of adenovirus type 37 infection of human corneal epithelial cells. Org Biomol Chem, 13, 9194-9205. PubMed id: 26177934 DOI: 10.1039/c5ob01025j

Date:

19-Jan-15 Release date: 29-Jul-15

Protein chains

Q64823  (Q64823_9ADEN) -  Fiber from Human adenovirus D37

Seq: 365 a.a.

Struc: 184 a.a.

DOI no: 10.1039/c5ob01025j

Org Biomol Chem 13:9194-9205 (2015)

PubMed id: 26177934

Triazole linker-based trivalent sialic acid inhibitors of adenovirus type 37 infection of human corneal epithelial cells.

R.Caraballo, M.Saleeb, J.Bauer, A.M.Liaci, N.Chandra, R.J.Storm, L.Frängsmyr, W.Qian, T.Stehle, N.Arnberg, M.Elofsson.

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.