3TAM

Crystal structure of HIV-1 reverse transcriptase (K103N mutant) in complex with inhibitor M06

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.51 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 

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Literature

Design and synthesis of pyridone inhibitors of non-nucleoside reverse transcriptase.

Gomez, R., Jolly, S., Williams, T., Tucker, T., Tynebor, R., Vacca, J., McGaughey, G., Lai, M.T., Felock, P., Munshi, V., DeStefano, D., Touch, S., Miller, M., Yan, Y., Sanchez, R., Liang, Y., Paton, B., Wan, B.L., Anthony, N.

(2011) Bioorg Med Chem Lett 21: 7344-7350

  • DOI: https://doi.org/10.1016/j.bmcl.2011.10.027
  • Primary Citation of Related Structures:  
    3TAM

  • PubMed Abstract: 

    Next generation NNRTIs are sought which possess both broad spectrum antiviral activity against key mutant strains and a high genetic barrier to the selection of new mutant viral strains. Pyridones were evaluated as an acyclic conformational constraint to replace the aryl ether core of MK-4965 (1) and the more rigid indazole constraint of MK-6186 (2). The resulting pyridone compounds are potent inhibitors of HIV RT and have antiviral activity in cell culture that is superior to other next generation NNRTI's.

    • Organizational Affiliation: 

    Department of West Point Discovery Chemistry, Merck Research Labs., 770 Sumneytown Pike, PO Box 4, West Point, PA 19486-0004, USA. Robert_gomez@merck.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Reverse transcriptase/ribonuclease H563HIV-1 M:B_HXB2RMutation(s): 1 
Gene Names: gag-pol, HIV-1
EC: 2.7.7.49 (PDB Primary Data), 2.7.7.7 (PDB Primary Data), 3.1.26.13 (PDB Primary Data), 3.1.13.2 (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 RT443HIV-1 M:B_HXB2RMutation(s): 1 
Gene Names: gag-pol, HIV-1
EC: 3.4.23.16 (PDB Primary Data), 2.7.7.49 (PDB Primary Data), 2.7.7.7 (PDB Primary Data), 3.1.26.13 (PDB Primary Data), 3.1.13.2 (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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
M06
Query on M06
Download Ideal Coordinates CCD File 
C [auth A]3-chloro-5-{[4-methyl-2-oxo-1-(2H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1,2-dihydropyridin-3-yl]oxy}benzonitrile
C20 H14 Cl N5 O2
YMRUCOCNLHJFRC-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
M06 PDBBind:  3TAM Ki: 3.7 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.51 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 117.91α = 90
b = 153.9β = 90
c = 155.69γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
BUSTERrefinement
HKL-2000data reduction
HKL-2000data scaling
BUSTERphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

  • Released Date: 2011-10-26 
    • Deposition Author(s): Yan, Y.

Revision History  (Full details and data files)

  • Version 1.0: 2011-10-26
    Type: Initial release
  • Version 1.1: 2012-01-18
    Changes: Database references
  • Version 1.2: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description