5UV5 | pdb_00005uv5

Crystal Structure of a 2-Hydroxyisoquinoline-1,3-dione RNase H Active Site Inhibitor with Multiple Binding Modes to HIV Reverse Transcriptase

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 
    0.287 (Depositor), 0.290 (DCC) 
  • R-Value Work: 
    0.232 (Depositor), 0.230 (DCC) 
  • R-Value Observed: 
    0.235 (Depositor) 

Starting Model: experimental
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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted Y55Click on this verticalbar to view details

This is version 1.4 of the entry. See complete history. 


Literature

A 2-Hydroxyisoquinoline-1,3-Dione Active-Site RNase H Inhibitor Binds in Multiple Modes to HIV-1 Reverse Transcriptase.

Kirby, K.A., Myshakina, N.A., Christen, M.T., Chen, Y.L., Schmidt, H.A., Huber, A.D., Xi, Z., Kim, S., Rao, R.K., Kramer, S.T., Yang, Q., Singh, K., Parniak, M.A., Wang, Z., Ishima, R., Sarafianos, S.G.

(2017) Antimicrob Agents Chemother 61

  • DOI: https://doi.org/10.1128/AAC.01351-17
  • Primary Citation of Related Structures:  
    5UV5

  • PubMed Abstract: 

    The RNase H (RNH) function of HIV-1 reverse transcriptase (RT) plays an essential part in the viral life cycle. We report the characterization of YLC2-155, a 2-hydroxyisoquinoline-1,3-dione (HID)-based active-site RNH inhibitor. YLC2-155 inhibits both polymerase (50% inhibitory concentration [IC 50 ] = 2.6 μM) and RNH functions (IC 50 = 0.65 μM) of RT but is more effective against RNH. X-ray crystallography, nuclear magnetic resonance (NMR) analysis, and molecular modeling were used to show that YLC2-155 binds at the RNH-active site in multiple conformations.

    • Organizational Affiliation: 

    Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA kirbyk@missouri.edu sarafianoss@missouri.edu.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Reverse transcriptase/ribonuclease H
A, C
557Human immunodeficiency virus type 1 BH10Mutation(s): 1 
Gene Names: gag-pol
EC: 2.7.7.49 (PDB Primary Data), 2.7.7.7 (PDB Primary Data), 3.1.26.13 (PDB Primary Data)
UniProt
Find proteins for P03366 (Human immunodeficiency virus type 1 group M subtype B (isolate BH10))
Explore P03366 
Go to UniProtKB:  P03366
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03366
Sequence Annotations
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  • Reference Sequence
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(by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
p51 RT
B, D
429Human immunodeficiency virus type 1 BH10Mutation(s): 1 
Gene Names: gag-pol
UniProt
Find proteins for P03366 (Human immunodeficiency virus type 1 group M subtype B (isolate BH10))
Explore P03366 
Go to UniProtKB:  P03366
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03366
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free:  0.287 (Depositor), 0.290 (DCC) 
  • R-Value Work:  0.232 (Depositor), 0.230 (DCC) 
  • R-Value Observed: 0.235 (Depositor) 
Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.99α = 105.53
b = 88.67β = 93.41
c = 108.86γ = 110.13
Software Package:
Software NamePurpose
Aimlessdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
XDSdata reduction

Structure Validation

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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted Y55Click on this verticalbar to view details

View more in-depth experimental data
Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI100890

Revision History  (Full details and data files)

  • Version 1.0: 2017-08-16
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Author supporting evidence
  • Version 1.2: 2017-10-04
    Changes: Database references
  • Version 1.3: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.4: 2023-10-04
    Changes: Data collection, Database references, Derived calculations, Refinement description