4NYF

HIV integrase in complex with inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.201 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history. 


Literature

Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1.

Fader, L.D., Malenfant, E., Parisien, M., Carson, R., Bilodeau, F., Landry, S., Pesant, M., Brochu, C., Morin, S., Chabot, C., Halmos, T., Bousquet, Y., Bailey, M.D., Kawai, S.H., Coulombe, R., LaPlante, S., Jakalian, A., Bhardwaj, P.K., Wernic, D., Schroeder, P., Amad, M., Edwards, P., Garneau, M., Duan, J., Cordingley, M., Bethell, R., Mason, S.W., Bos, M., Bonneau, P., Poupart, M.A., Faucher, A.M., Simoneau, B., Fenwick, C., Yoakim, C., Tsantrizos, Y.

(2014) ACS Med Chem Lett 5: 422-427

  • DOI: https://doi.org/10.1021/ml500002n
  • Primary Citation of Related Structures:  
    4NYF

  • PubMed Abstract: 

    An assay recapitulating the 3' processing activity of HIV-1 integrase (IN) was used to screen the Boehringer Ingelheim compound collection. Hit-to-lead and lead optimization beginning with compound 1 established the importance of the C3 and C4 substituent to antiviral potency against viruses with different aa124/aa125 variants of IN. The importance of the C7 position on the serum shifted potency was established. Introduction of a quinoline substituent at the C4 position provided a balance of potency and metabolic stability. Combination of these findings ultimately led to the discovery of compound 26 (BI 224436), the first NCINI to advance into a phase Ia clinical trial.

    • Organizational Affiliation: 

    Research and Development, Boehringer Ingelheim (Canada) Ltd. , 2100 Cunard Street, Laval, Québec H7S 2G5, Canada.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Integrase
A, B
168Human immunodeficiency virus type 1 lw12.3 isolateMutation(s): 4 
Gene Names: gag-pol
EC: 2.7.7
UniProt
Find proteins for P0C6F2 (Human immunodeficiency virus type 1 group M subtype B (isolate LW123))
Explore P0C6F2 
Go to UniProtKB:  P0C6F2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0C6F2
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
4BI BindingDB:  4NYF Kd: 49 (nM) from 1 assay(s)
Binding MOAD:  4NYF Kd: 49 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.201 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 59.77α = 90
b = 62.45β = 90
c = 81.32γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
MAR345dtbdata collection
HKL-2000data reduction
HKL-2000data scaling
CNXphasing
CNXrefinement

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: 2014-06-25
    Type: Initial release
  • Version 1.1: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description