6NAE

Crystal Structure of Ebola zaire GP protein with bound ARN0074898

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.197 

Starting Model: experimental
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This is version 2.2 of the entry. See complete history. 


Literature

Discovery of Adamantane Carboxamides as Ebola Virus Cell Entry and Glycoprotein Inhibitors.

Plewe, M.B., Sokolova, N.V., Gantla, V.R., Brown, E.R., Naik, S., Fetsko, A., Lorimer, D.D., Dranow, D.M., Smutney, H., Bullen, J., Sidhu, R., Master, A., Wang, J., Kallel, E.A., Zhang, L., Kalveram, B., Freiberg, A.N., Henkel, G., McCormack, K.

(2020) ACS Med Chem Lett 11: 1160-1167

  • DOI: https://doi.org/10.1021/acsmedchemlett.0c00025
  • Primary Citation of Related Structures:  
    6NAE

  • PubMed Abstract: 

    We identified and explored the structure-activity-relationship (SAR) of an adamantane carboxamide chemical series of Ebola virus (EBOV) inhibitors. Selected analogs exhibited half-maximal inhibitory concentrations (EC 50 values) of ∼10-15 nM in vesicular stomatitis virus (VSV) pseudotyped EBOV (pEBOV) infectivity assays, low hundred nanomolar EC 50 activity against wild type EBOV, aqueous solubility >20 mg/mL, and attractive metabolic stability in human and nonhuman liver microsomes. X-ray cocrystallographic characterizations of a lead compound with the EBOV glycoprotein (GP) established the EBOV GP as a target for direct compound inhibitory activity and further provided relevant structural models that may assist in identifying optimized therapeutic candidates.

    • Organizational Affiliation: 

    Arisan Therapeutics, 11189 Sorrento Valley Road, Suite 104, San Diego, California 92121, United States.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein,Envelope glycoprotein,Envelope glycoprotein330Ebola virus - Mayinga, Zaire, 1976Mutation(s): 1 
Gene Names: GP
UniProt
Find proteins for Q05320 (Zaire ebolavirus (strain Mayinga-76))
Explore Q05320 
Go to UniProtKB:  Q05320
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ05320
Glycosylation
Glycosylation Sites: 4
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein168Ebola virus - Mayinga, Zaire, 1976Mutation(s): 1 
Gene Names: GP
UniProt
Find proteins for Q05320 (Zaire ebolavirus (strain Mayinga-76))
Explore Q05320 
Go to UniProtKB:  Q05320
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ05320
Glycosylation
Glycosylation Sites: 1
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22768VO
GlyCosmos:  G22768VO
GlyGen:  G22768VO
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
KHG
Query on KHG
Download Ideal Coordinates CCD File 
K [auth A](1S,3R,5R,7S)-N-(trans-4-aminocyclohexyl)-3-methyl-5-phenyltricyclo[3.3.1.1~3,7~]decane-1-carboxamide
C24 H34 N2 O
TZNRCHUCVIMHIH-UCWUHLBISA-N
NAG
Query on NAG
Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
G [auth A]		2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
GOL
Query on GOL
Download Ideal Coordinates CCD File 
H [auth A],
I [auth A],
J [auth A],
L [auth A],
M [auth B]		GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.197 
  • Space Group: H 3 2
  • Diffraction Data: https://doi.org/10.18430/m36nae
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 113.25α = 90
b = 113.25β = 90
c = 307.21γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-12-11
    Type: Initial release
  • Version 1.1: 2019-12-25
    Changes: Database references
  • Version 1.2: 2020-07-01
    Changes: Data collection, Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-10-11
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary
  • Version 2.2: 2024-11-20
    Changes: Structure summary