3DCK

X-ray structure of D25N chemical analogue of HIV-1 protease complexed with ketomethylene isostere inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 

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This is version 1.6 of the entry. See complete history. 


Literature

Crystal structure of chemically synthesized HIV-1 protease and a ketomethylene isostere inhibitor based on the p2/NC cleavage site

Torbeev, V.Y., Mandal, K., Terechko, V.A., Kent, S.B.H.

(2008) Bioorg Med Chem Lett 18: 4554-4557

  • DOI: https://doi.org/10.1016/j.bmcl.2008.07.039
  • Primary Citation of Related Structures:  
    3DCK, 3DCR

  • PubMed Abstract: 

    Here we report the X-ray structures of chemically synthesized HIV-1 protease and the inactive [D25N]HIV-1 protease complexed with the ketomethylene isostere inhibitor Ac-Thr-Ile-Nle psi[CO-CH(2)]Nle-Gln-Arg.amide at 1.4 and 1.8A resolution, respectively. In complex with the active enzyme, the keto-group was found to be converted into the hydrated gem-diol, while the structure of the complex with the inactive D25N enzyme revealed an intact keto-group. These data support the general acid-general base mechanism for HIV-1 protease catalysis.

    • Organizational Affiliation: 

    Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. torbeev@uchicago.edu


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Chemical analogue HIV-1 protease
A, B
99N/AMutation(s): 0 
EC: 3.4.23.16
UniProt
Find proteins for O38732 (Human immunodeficiency virus 1)
Explore O38732 
Go to UniProtKB:  O38732
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO38732
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
KVI
Query on KVI
Download Ideal Coordinates CCD File 
C [auth B](2S)-2-{[(2R,5S)-5-{[(2S,3S)-2-{[(2S,3R)-2-(acetylamino)-3-hydroxybutanoyl]amino}-3-methylpentanoyl]amino}-2-butyl-4-oxononanoyl]amino}-N~1~-[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]pentanediamide
C36 H66 N10 O9
ARYLRJRVHGPIHO-XPRREXDTSA-N
Modified Residues  3 Unique
IDChains TypeFormula2D DiagramParent
ABA
Query on ABA
A, B
L-PEPTIDE LINKINGC4 H9 N O2ALA
NLE
Query on NLE
A, B
L-PEPTIDE LINKINGC6 H13 N O2LEU
YCM
Query on YCM
A, B
L-PEPTIDE LINKINGC5 H10 N2 O3 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.028α = 90
b = 58.551β = 90
c = 61.584γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

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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: Advisory, Version format compliance
  • Version 1.2: 2013-10-16
    Changes: Non-polymer description
  • Version 1.3: 2017-10-25
    Changes: Refinement description
  • Version 1.4: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.5: 2023-11-15
    Changes: Data collection
  • Version 1.6: 2024-03-20
    Changes: Source and taxonomy, Structure summary