4K6U

Crystal structure of Ad37 fiber knob in complex with trivalent sialic acid inhibitor ME0386


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.178 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.6 of the entry. See complete history


Literature

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

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

(2015) Org Biomol Chem 13: 9194-9205

  • DOI: https://doi.org/10.1039/c5ob01025j
  • Primary Citation of Related Structures:  
    4K6T, 4K6U, 4K6V, 4K6W, 4XQA, 4XQB

  • 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.


  • Organizational Affiliation

    Department of Chemistry, Umeå University, SE90187 Umeå, Sweden. [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fiber protein
A, B, C
194Human adenovirus D37Mutation(s): 0 
Gene Names: L5
UniProt
Find proteins for Q64823 (Human adenovirus D37)
Explore Q64823 
Go to UniProtKB:  Q64823
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ64823
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1P4
Query on 1P4

Download Ideal Coordinates CCD File 
H [auth B]3,3',3''-[nitrilotris(methanediyl-1H-1,2,3-triazole-4,1-diyl)]tripropan-1-ol
C18 H30 N10 O3
VAKXPQHQQNOUEZ-UHFFFAOYSA-N
SIA
Query on SIA

Download Ideal Coordinates CCD File 
E [auth A],
G [auth B],
J [auth C]
N-acetyl-alpha-neuraminic acid
C11 H19 N O9
SQVRNKJHWKZAKO-YRMXFSIDSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
D [auth A],
F [auth B],
I [auth C]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
K [auth C]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.178 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.86α = 90
b = 69.91β = 94.62
c = 74.07γ = 90
Software Package:
Software NamePurpose
RemDAqdata collection
PHASERphasing
REFMACrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-10-22
    Type: Initial release
  • Version 1.1: 2015-07-29
    Changes: Database references
  • Version 1.2: 2015-09-09
    Changes: Database references
  • Version 1.3: 2017-11-15
    Changes: Refinement description
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Database references, Derived calculations, Structure summary
  • Version 1.5: 2024-02-28
    Changes: Data collection, Database references, Structure summary
  • Version 1.6: 2024-04-03
    Changes: Refinement description