3DI6

HIV-1 RT with pyridazinone non-nucleoside inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.217 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Discovery and optimization of pyridazinone non-nucleoside inhibitors of HIV-1 reverse transcriptase.

Sweeney, Z.K., Dunn, J.P., Li, Y., Heilek, G., Dunten, P., Elworthy, T.R., Han, X., Harris, S.F., Hirschfeld, D.R., Hogg, J.H., Huber, W., Kaiser, A.C., Kertesz, D.J., Kim, W., Mirzadegan, T., Roepel, M.G., Saito, Y.D., Silva, T.M., Swallow, S., Tracy, J.L., Villasenor, A., Vora, H., Zhou, A.S., Klumpp, K.

(2008) Bioorg Med Chem Lett 18: 4352-4354

  • DOI: https://doi.org/10.1016/j.bmcl.2008.06.072
  • Primary Citation of Related Structures:  
    3DI6

  • PubMed Abstract: 

    A series of benzyl pyridazinones were evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Several members of this series showed good activity against the wild-type virus and NNRTI-resistant viruses. The binding of inhibitor 5a to HIV-RT was analyzed by surface plasmon resonance spectroscopy. Pharmacokinetic studies of 5a in rat and dog demonstrated that this compound has good oral bioavailability in animal species. The crystal structure of a complex between HIV-RT and inhibitor 4c is also described.

    • Organizational Affiliation: 

    Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. zachary.sweeney@roche.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Reverse transcriptase/ribonuclease H561HIV-1 M:B_HXB2RMutation(s): 0 
Gene Names: gag-pol
EC: 2.7.7.49 (PDB Primary Data), 2.7.7.7 (PDB Primary Data), 3.1.26.4 (PDB Primary Data)
UniProt
Find proteins for P04585 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04585 
Go to UniProtKB:  P04585
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04585
Sequence Annotations
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  • Reference Sequence
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
p51 RT440HIV-1 M:B_HXB2RMutation(s): 0 
Gene Names: gag-pol
UniProt
Find proteins for P04585 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04585 
Go to UniProtKB:  P04585
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04585
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PDZ
Query on PDZ
Download Ideal Coordinates CCD File 
C [auth A]6-(4-chloro-2-fluoro-3-phenoxybenzyl)pyridazin-3(2H)-one
C17 H12 Cl F N2 O2
NOVPOXGMADEKPP-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
PDZ PDBBind:  3DI6 IC50: 100 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.217 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 117.046α = 90
b = 153.51β = 90
c = 154.551γ = 90
Software Package:
Software NamePurpose
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

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: 2008-08-19
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations